Complemento de Seminario 3 Integración de células en tejidos - Gabriel Scicolone

Integration of Cells in Tissues

Overview of Course Structure

• The session begins with an introduction by the speaker, who is joined by Sofía and Lautaro to discuss the conceptual synthesis regarding cell integration into tissues.

• The first block covered cellular command, focusing on how the nucleus regulates cellular functions, along with seminars on molecular biology techniques.

• In the second block, topics included cytoplasmic functions, macromolecule distribution, cytoskeleton dynamics, and bioenergetics with a focus on mitochondria.

Transition to Multicellular Organisms

• The third block shifts focus to how cells function within multicellular organisms, integrating cellular structure and function with that of the entire organism.

• Upcoming classes will cover intracellular signaling, cellular differentiation in multicellular organisms, tumor cell populations, and programmed cell death.

Objectives of Today's Class

• Key objectives include describing how cellular populations organize into tissues and maintaining this organization.

• Recognition of extracellular matrix components and comparison between epithelial and non-epithelial tissue organization will be emphasized.

• Identification of adhesion molecules involved in cell-cell interactions and their regulatory roles will also be discussed.

Cellular Organization in Multicellular Organisms

• Cells in multicellular organisms cooperate to form structures with specific functions known as tissues—this represents a higher level of organization than individual cells.

• Tissues further organize into organs which then associate to form systems or apparatuses within an organism.

Types of Tissues

• Four basic tissue types are identified: epithelial tissue (e.g., cuboidal or columnar), connective tissue (including specialized forms like cartilage), muscular tissue, and nervous tissue.

• Focus today will be on structural organization within epithelial tissues compared to connective tissues.

Structural Relationships Between Tissues

• A comparative analysis will highlight differences between epithelial (high cell density; limited extracellular matrix; intercellular relationships are predominant) versus connective tissues (lower cell density; abundant extracellular matrix).

• Epithelial tissues often limit spaces (lumen), while connective tissues do not have such limitations due to their extensive extracellular matrix composition.

Understanding Tissue Stability and Cell Communication

Overview of Tissue Dynamics

• In tissues, there are cells that renew, die, and proliferate; however, this cellular turnover does not disrupt the overall organization of the tissue.

• The discussion shifts from solely focusing on cells to including extracellular matrix (ECM), which is essential for multicellular organisms as cells must secrete ECM for structural integrity.

Components of Tissues

• Tissues consist of two main components: cells and the extracellular matrix. Their interaction is crucial for maintaining tissue structure.

• Despite ongoing renewal processes in both cellular and intercellular components, tissues maintain structural and functional stability due to several factors.

Factors Maintaining Tissue Stability

• Key factors contributing to tissue stability include:

• Cell Communication: Coordinates cell functions and supports tissue stability.

• Selective Adhesion: Differential adhesion between cells and ECM helps maintain tissue integrity.

Cellular Memory and Niches

• Cellular memory allows cells to retain gene expression patterns over time, preserving tissue characteristics.

• Cellular niches refer to microenvironments where stem or progenitor cells reside, playing a vital role in maintaining stability.

Molecules of Adhesion in Tissue Integrity

Types of Adhesion Molecules

• A series of molecules known as adhesion molecules facilitate cell-to-cell and cell-to-matrix interactions.

• These molecules can be classified into two types based on their binding nature:

• Homophilic Interactions: Similar molecules bind together (e.g., cadherins).

• Heterophilic Interactions: Different types of molecules interact with each other.

Cadherins

• Cadherins form stable homodimers that require calcium ions for strong adhesion between neighboring cells. Their function is influenced by extracellular calcium concentration.

CAM Molecules

Intercellular Adhesion Molecules and Their Functions

Types of Adhesion Molecules

• The transcript discusses two groups of adhesion molecules involved in heterophilic interactions: integrins and selectins. Integrins are heterodimers composed of alpha and beta peptides that interact with extracellular matrix components.

• Integrins have various combinations, allowing them to bind to different extracellular matrix components like fibronectin, facilitating cell-matrix adhesion.

• Selectins are membrane glycoproteins that mediate transient intercellular adhesion by binding to neighboring cell glycoproteins, highlighting their role in temporary heterophilic interactions.

Stability and Duration of Adhesions

• Among the three types of intercellular junctions discussed (cadherins, CAMs, selectins), cadherin connections are the most stable, while selectin connections are the most transient.

• Integrins can also form heterophilic bonds with CAM family members, indicating a complex interplay between different adhesion molecules in cellular interactions.

Role in Cellular Anchoring

• These adhesion molecules play crucial roles in anchoring cells together or connecting them to the extracellular matrix (ECM), particularly evident in epithelial tissues and synapses.

• When large aggregates of these molecules form visible structures under optical or electron microscopy, they create what is known as anchoring junctions between cells or between cells and ECM.

Mechanisms of Cell Interaction

• The term "anchoring junction" refers to how these molecules allow a cell's cytoskeleton to indirectly anchor itself either to another cell's cytoskeleton or directly to the ECM.

• There are two main types of anchoring junctions observable under electron microscopy: those involving direct cell-to-cell interaction and those linking cells with ECM.

Types of Anchoring Junctions

• Anchoring junction types depend on which cytoskeletal components they connect; for instance:

• Actin filaments link through adherens junctions.

• Intermediate filaments connect via desmosomes.

• Adherens junctions relate actin filaments between adjacent cells while desmosomes connect intermediate filaments.

Additional Junction Types

• In addition to intercellular anchoring mechanisms, there are also focal adhesions that link actin filaments with ECM components. Hemidesmosomes serve a similar function but involve intermediate filaments connecting with ECM.

Cellular Junctions and Communication

Types of Cellular Junctions

• Gap Junctions: These are channels that allow the passage of small molecules between adjacent cells, facilitating coordination among neighboring cells.

• Signaling Junctions: While other junction types also involve signaling, these junctions primarily focus on communication. Examples include chemical synapses in the nervous system and immunological synapses formed between lymphocytes.

• Transmembrane Receptor-Ligand Interactions: This group includes molecules like Delta and Ephrin, which play roles in intercellular anchoring and signaling processes.

Mechanisms of Cell Communication

• Differential Adhesion: Molecular mechanisms that ensure functional and structural stability within tissues. An example is simple columnar epithelium found in the small intestine, showcasing various junction types along its basolateral membrane.

• Types of Junctional Structures:

• Tight Junctions (Oclusivas): Form a belt-like structure preventing leakage.

• Adherens Junctions: Connect to actin filaments.

• Desmosomes: Link intermediate filaments (specifically cytokeratin in epithelial tissue).

Importance of Gap Junctions

• Functionality in Cardiac Tissue: Gap junctions are crucial for synchronizing muscle fiber contractions in cardiac tissue by allowing rapid communication between cells.

Components of Anchoring Junctions

• Basic Structure:

• Composed of adhesion proteins or glycoproteins (transmembrane proteins).

• Anchoring proteins facilitate interaction with cytoskeletal components.

• Adhesion Molecules in Different Junction Types:

• Adherens junction involves classical cadherins.

• Desmosomes utilize non-classical cadherins for cell-cell adhesion.

Interaction with Cytoskeleton

• Cytoskeletal Connections:

• In adherens junction, intracellular anchoring proteins connect cadherins to actin filaments.

• In desmosomes, adhesion molecules interact with intermediate filaments through specific intracellular anchoring proteins.

Integrins and Extracellular Matrix Interactions

• Integrin Functionality:

• Integrins mediate stable connections with the extracellular matrix (ECM), forming focal adhesions where actin filaments link to ECM components.

• Diverse Roles of Integrins:

• Different integrin types relate either directly or indirectly to intermediate filaments within the ECM context.

Cadherin Diversity Across Tissues

• Cadherin Variants and Their Locations:

• E-cadherin predominates in epithelial tissues; N-cadherin is prevalent in neurons and muscle fibers; P-cadherin is found mainly in epidermis and mammary glands; B-cadherins are associated with endothelial tissues.

• Non-Classical Cadherins' Role:

Understanding Cadherins and Cell Adhesion

Cadherin Types and Their Interactions

• The discussion begins with a diagram illustrating anchoring junctions, highlighting cadherins (specifically E-cadherins) and their connection to actin filaments via catenins, which are anchoring proteins.

• It is noted that E-cadherins interact with other E-cadherins, while N-cadherins only interact with fellow N-cadherins. There is no interaction between different types of cadherins.

Role in Cellular Signaling

• Cadherin interactions are not solely mechanical; they also play a role in intercellular signaling. This adhesion leads to intracellular signals that can alter cell behavior, indicating a duality between adhesion and communication.

Differential Expression in Development

• The transcript discusses the differential distribution of various cadherin types (E, R, 6), emphasizing how this variation facilitates cell aggregation within specific regions while preventing cells from different areas from adhering to one another.

• Experiments show that when cells expressing different cadherins are mixed in vitro, they segregate into distinct groups based on their cadherin type, demonstrating the importance of these molecules in maintaining cellular organization.

Implications for Neural Development

• High expression levels of E-cadherin are observed in ectodermal cells during neural tube formation. As invagination occurs, cells forming the neural groove express primarily N-cadherin.

• Cells at the boundary between general ectoderm (expressing E-cadherin) and neuroepithelium (expressing N-cadherin) begin to express Caderina 6b as development progresses towards neural crest formation.

Transition from Epithelial to Mesenchymal Cells

• A significant transformation occurs where epithelial cells lose their intercellular adhesion due to changes in cadherin expression and transition into mesenchymal cells capable of migration.

• In more developed stages, variations in cadherin expression continue to be crucial for maintaining structural integrity within the developing nervous system while allowing for necessary cellular migrations.

Summary of Cadherin Functions

• The differential expression of cadherins allows for cellular aggregation essential for developmental processes. This segregation helps form compartments where different cell types adhere together effectively.

• While cadherins play a vital role in these phenomena, it is acknowledged that they are not the sole molecules involved; however, they significantly contribute to compartmentalization during development.

Cellular Morphology and Neural Tube Formation

Changes in Cell Shape

• The contraction of actin filaments causes the apical part of cells to narrow, transforming cylindrical cells into pyramidal shapes, leading to epithelial invagination.

• Continued invagination can result in the separation of a vesicular structure from ectodermal epithelium, forming the neural tube.

Role of Cell Adhesion and Cytoskeleton

• Intercellular junctions not only provide mechanical anchorage but also facilitate intracellular signaling that influences gene expression.

• This interaction creates a feedback loop where cellular interactions modify gene expression patterns, affecting adhesion molecule types and quantities expressed by cells.

Gene Expression Regulation

• Signals from neighboring cells and the microenvironment are crucial for regulating gene expression, which in turn alters cell communication through adhesion molecules.

• The interplay between adhesion molecules on cell surfaces and gene regulation is essential for maintaining proper cellular functions.

Types of Intercellular Junctions

Adherens Junctions

• Adherens junctions involve actin filament dynamics that enable epithelial invagination by reducing the size of the apical region of cells.

Desmosomes: Structure and Function

• Desmosomes connect intermediate filaments (like keratin) between adjacent cells using non-classical cadherins such as desmoglein and desmocolin.

• These junctions play a critical mechanical role by providing tensile strength through their connection with intermediate filaments.

Mechanical Properties and Pathologies

Impact of Keratin Mutations

• Mutations in keratin genes can lead to weakened cell connections under stress, resulting in conditions like blistering when minor trauma occurs.

Example: Epidermolysis Bullosa Simplex

• This condition arises from mutations affecting intermediate filament integrity, causing large blisters due to reduced tensile strength within epithelial layers.

Extracellular Matrix Interactions

Hemidesmosomes and Focal Adhesions

• Hemidesmosomes anchor epithelial cells to the extracellular matrix (ECM), while focal adhesions link actin filaments to ECM components.

Structure of Basal Membrane

• The basal membrane consists mainly of two parts: lamina basalis (secreted by epithelium) and lamina reticularis (produced by connective tissue).

Integrins as Adhesion Molecules

Adhesion Mechanisms in Cellular Biology

Integrins and Extracellular Matrix Interaction

• Integrins play a crucial role in cell adhesion to the extracellular matrix (ECM), with varying combinations affecting their affinity for different ECM components.

• Hemidesmosomes are formed by integrins binding to anchoring proteins and intermediate filaments, providing structural support and resistance to cellular traction.

• Focal adhesions involve distinct integrins that interact with actin filaments, facilitating transient connections during cell migration, particularly in mesenchymal cells like fibroblasts or macrophages.

Mechanisms of Cell Migration

• During migration, integrins connect to the ECM through focal contacts, allowing actin filaments to exert force via myosin II, leading to cellular retraction at the rear.

• The activity of integrins is influenced by magnesium levels; inactive integrins can become coiled and non-functional until activated for ECM anchorage.

Signaling Pathways Influenced by Adhesion

• Active integrins not only anchor cells but also participate in intracellular signaling pathways that can alter cytoskeletal dynamics and gene expression.

• Changes in gene expression may affect the types of heterodimers expressed on a cell's surface, influencing its adhesive properties.

Adhesion and Deadhesion Dynamics

• Cells can undergo deadhesion processes; epithelial cells typically exhibit strong intercellular interactions while mesenchymal cells have more transient ECM connections.

• Epithelial-to-mesenchymal transition (EMT) allows epithelial cells to migrate as they reduce adhesion levels—this is significant in tumor progression.

Developmental Processes Involving Cell Adhesion

• Neural crest cells transition from an epithelial state (high adhesion via cadherins) to a migratory mesenchymal state by degrading the basal lamina.

• This transition illustrates how high adhesion states can shift towards lower adhesion states during development or pathological conditions like cancer invasion.

Importance of Adhesion Molecule Regulation

• Regulating adhesion molecules is vital for transitioning between epithelial and mesenchymal phenotypes, impacting both normal developmental processes and abnormal tumor invasiveness.

• Examples include white blood cells adhering transiently to endothelial cells during inflammation through selectin-glycoprotein interactions that activate integrin-mediated rolling.

Cell Adhesion and Communication Mechanisms

Integrins and Cell Migration

• Integrins form heterophilic intercellular connections that are more durable than those formed by selectins, allowing blood cells to migrate between endothelial cells into connective tissue.

Cellular Polarization in Inflammation

• During inflammation, cells increase their polarity, extending leading edges (lamellipodia and filopodia) while retracting the rear. This process involves adhesion molecules organized at the front and disorganized at the back.

Actin Dynamics in Cell Movement

• The anterior part of the cell experiences actin filament polymerization, while depolymerization occurs at the posterior end due to myosin sliding, facilitating cellular retraction.

Adhesion Molecules in Synapses

• Adhesion molecules play a crucial role in synaptic communication between neurons, linking presynaptic axons with postsynaptic dendrites or other cell types through cadherins and CAM proteins.

Structure of Synaptic Connections

• The synapse consists of presynaptic terminals and postsynaptic dendrites held together by adhesion molecules that connect their actin cytoskeletons across an extracellular matrix space.

Types of Cell Junctions

Occluding Junctions: Tight Junctions

• Tight junctions are formed by transmembrane proteins called occludins and claudins that prevent molecular passage between epithelial cells, maintaining barrier integrity.

Functions of Tight Junctions

• These junctions not only block molecule movement but also preserve membrane polarity by preventing apical membrane components from mixing with basolateral membranes.

Visualization of Tight Junction Functionality

• Electron microscopy can reveal tight junction effectiveness; tracers do not pass through intercellular spaces due to these junctional belts formed by multiple tight junction strands.

Gap Junction Communication

Structure and Function of Gap Junctions

• Gap junction channels consist of connexons made up of six protein subunits each, allowing small molecules to pass directly between adjacent cells for synchronized function.

Importance in Cardiac Muscle Functionality

Cellular Mechanisms and Extracellular Matrix

Cellular Communication and Adhesion

• The mechanisms involved in maintaining structural and functional stability of tissues include cellular communication and selective cell adhesion, highlighting the role of adhesion molecules.

• Adhesion molecules can participate in adhesion and disadhesion phenomena without forming classical junctions typically described in epithelial cells, particularly not in mesenchymal cells.

Intercellular Junctions

• Discussion on types of intercellular junctions includes communication junctions that allow passage of molecules between cells, contrasting with chemical synapses where cytosolic communication does not occur.

• In chemical synapses, neurotransmitter vesicles release components that bind to receptors, leading to conformational changes for cellular signaling without direct cytosolic exchange.

Synaptic Structures

• Synapses are specialized structures facilitating interaction between two cell parts for signaling; they differ from communicating junctions as they do not allow direct cytoplasmic flow.

• Communicating junctions enable molecular passage between adjacent cell cytosols, while synapses (chemical or electrical) serve distinct roles based on their classification criteria.

Types of Synapses

• Chemical synapses involve communication through the release of chemical substances from one terminal to another, whereas electrical synapses (communicating junctions) allow ion passage affecting membrane charge.

• Electrical synapses are prevalent in embryonic nervous tissue and muscle tissue; they facilitate rapid ionic exchanges crucial for communication.

Classification of Junctional Types

• Depending on classification criteria, synapses can be categorized into chemical or electrical types; communicating junction examples include both types due to their molecular transfer capabilities.

• The classification is flexible; anchoring junction types also play a role in signaling despite being primarily defined by their anchoring function.

Extracellular Matrix Dynamics

• Transitioning to extracellular matrix (ECM), which is vital for tissue stability and dynamics. ECM is abundant in connective tissues and has specialized forms like the basal lamina.

Understanding the Components of Extracellular Matrix

Structural Proteins and Their Functions

• The extracellular matrix (ECM) is maintained by structural proteins like collagen and fibrillin, which provide mechanical support to tissues.

• Fibrillin, a component of elastic fibers along with elastin, plays a crucial role in maintaining tissue elasticity.

• Specialized proteins such as growth factors regulate cellular processes including cell cycle and differentiation; metalloproteinases degrade ECM components.

• Proteoglycans and glycosaminoglycans are significant ECM components; proteoglycans consist of protein cores with carbohydrate chains that influence cell signaling.

• Mechanical resistance in connective tissues primarily relies on the ECM rather than cells, highlighting its regulatory functions.

Classification of ECM Components

• The classification of ECM components includes structural proteins for mechanical function, specialized proteins for cellular regulation, and distinct categories for proteoglycans and glycosaminoglycans due to their unique structures.

• Histologically, ECM can be categorized into fibers (like collagen and elastin) and amorphous substance; non-fibrous structural proteins also contribute to the amorphous matrix.

Importance of Basal Lamina

• In epithelial tissues, mechanical support is provided by cytokeratin filaments while the basal lamina serves as a specialized ECM structure essential for adhesion.

• All epithelia possess a basal lamina composed of various ECM components including type IV collagen forming a network structure.

Composition of Basal Lamina

• The basic structure of the basal lamina includes type IV collagen networks, laminin (an adhesion glycoprotein), perlecan (a proteoglycan), and entactin (another adhesion molecule).

• These components interact to form a mesh-like structure that supports epithelial cells through integrins.

Overview of Fibronectin and Proteoglycans

• Fibronectin is classified as a specialized protein crucial for cell adhesion; it consists of two polypeptides linked by disulfide bonds facilitating interactions with integrins.

• Fibronectin interacts with other ECM elements like collagens and proteoglycans to aid in cellular organization within the matrix.

• Proteoglycans are macromolecular complexes formed from protein cores covalently bonded to linear carbohydrates known as glycosaminoglycans.

Proteoglycans and Glycoproteins: Key Differences

Understanding Proteoglycans

• Proteoglycans are complex molecules formed from polysaccharides, which can be of multiple types. They differ from glycoproteins, where the primary component is a protein with small branched carbohydrate groups attached.

• In glycoproteins, the main structure is the protein itself, while in proteoglycans, unbranched carbohydrates (glycosaminoglycans) covalently bond to a protein core.

Types of Glycosaminoglycans

• Glycosaminoglycans include various forms; for instance, hyaluronic acid is a disaccharide that does not covalently attach to proteins but interacts non-covalently with other proteoglycans.

• Glycosaminoglycans are classified into two groups: those forming part of proteoglycans (which bind covalently to proteins) and those like hyaluronic acid that exist as free chains.

Structural Role in Tissues

• Hyaluronic acid and associated proteoglycans create a three-dimensional mesh-like structure that attracts water and ions, facilitating cellular migration within connective tissues rich in these components.

• These structures are abundant in loose connective tissues and mucous connective tissue, which resemble embryonic mesenchyme due to their high content of glycosaminoglycans.

Collagen Synthesis: A Detailed Overview

Collagen Structure and Formation

• Collagen synthesis involves polypeptide chains that coil together into triple helices known as tropocollagen. This process begins in the rough endoplasmic reticulum where proteins undergo post-translational modifications.

• Tropocollagen is secreted into the extracellular matrix as pro-collagen, which contains additional segments that will later be cleaved by enzymes to form mature collagen.

Fibril Organization

• Mature collagen molecules aggregate through enzymatic action to form fibrils. Each fibril consists of numerous tropocollagen units arranged parallel yet slightly offset.

• Under electron microscopy, these fibrils display distinct banding patterns indicative of their structural organization.

Diversity of Collagen Types

Variability in Collagen Composition

• There are over 27 different types of collagen identified based on variations in the combinations of three polypeptide chains forming each molecule.

• More than 40 distinct chain types have been recognized; each type corresponds to specific genes responsible for encoding them.

Functional Implications

• Different collagen types serve unique functions; for example:

• Type I collagen forms fibers found predominantly in dermis,

• Type II collagen constitutes cartilage matrix,

Understanding the Structure and Function of Extracellular Matrix

Composition of the Extracellular Matrix

• The extracellular matrix (ECM) includes collagen fibers found in blood vessel walls, lymphatic organs, and endocrine glands, contributing to their structural integrity.

• Different types of collagen are categorized into those that form fibrils (e.g., type 2 and type 9) and those that do not; type 4 forms basal laminae while type 7 creates anchoring fibers in stratified epithelia like the epidermis.

• Collagen molecules play a crucial role in forming fibrils within the ECM, primarily synthesized by chondroblasts in cartilage tissue.

Functions of ECM Components

• All organic components of the ECM are synthesized and secreted by specific cells, providing mechanical strength through collagen while also participating in signaling processes via trophic factors.

• Fibronectin serves as an adhesion protein linking integrins on cell membranes to collagen fibers, proteoglycans, and hyaluronic acid within the ECM.

Interaction Between Cells and ECM

• The three major macromolecules—collagen (structural), fibronectin (adhesion glycoprotein), and proteoglycans—are essential for maintaining cellular structure and function within tissues.

• Integrins facilitate cell adhesion to laminins, fibronectin, and collagen; this interaction is vital for mechanical stability as well as intracellular signaling that can influence gene expression related to cell proliferation, differentiation, and migration.

Remodeling of the Extracellular Matrix

• The ECM is dynamic rather than static; it undergoes remodeling influenced by various cellular activities. For instance, bone matrix is more stable compared to non-specialized connective tissue due to its calcified nature.

• Enzymatic action plays a significant role in ECM remodeling. Two main groups include serine proteases (like plasminogen activators) and metalloproteinases which degrade matrix components.

Mechanisms of Degradation

• Metalloproteinases are secreted inactive but become activated extracellularly; they allow localized degradation around cells facilitating processes such as mesenchymal cell migration through temporary matrix breakdown.

• Plasminogen secreted by cells converts into plasmin which activates metalloproteinases leading to further degradation of ECM components. This cascade allows precise control over matrix remodeling.

Metaloproteinasas y su Rol en la Matriz Extracelular

Función de las Metaloproteinasas

• Las metaloproteinasas actúan al unirse a receptores específicos, participando en procesos como la transcripción, traducción, modificación post-traduccional y secreción. Estas enzimas pueden estar inactivas como cimógenas y son responsables de degradar componentes de la matriz extracelular.

• Existen diferentes tipos de metaloproteasas:

• Colagenasas: Degradan varios tipos de colágeno.

• Gelatinasa: Degradan gelatina, que es colágeno desnaturalizado.

• También degradan laminina y fibronectina, así como colágeno tipo IV.

Importancia en la Remodelación Celular

• La remodelación de la matriz extracelular es crucial para la progresión e invasión celular tumoral. Diferentes metaloproteasas degradan distintos componentes de esta matriz, facilitando cambios estructurales necesarios para el movimiento celular.

• Durante la transición epitelio-mesenquimática, las células epiteliales pierden moléculas de adhesión (como caderinas), alteran su citoesqueleto y secretan metaloproteasas que les permiten migrar al degradar la matriz extracelular.

Migración Celular Facilitada por Metaloproteasas

• Las células secretan activadores del plasminógeno que se unen a sus propios receptores, enfocando su acción sobre la matriz extracelular circundante para facilitar su migración.

• Los activadores del plasminógeno convierten el plasminógeno en plasmina, que degrada la matriz extracelular y activa más metaloproteasas. Esto es esencial para procesos como:

• Migración celular.

• Transición epitelio-mesenquimático.

Mecanismos Adicionales en Estabilidad Tejidos

• Se discuten tres mecanismos clave para mantener estabilidad estructural y funcional del tejido:

• Comunicación celular.

• Adhesión diferencial.

• Síntesis e interacción con componentes de la matriz extracelular.

• Se mencionan dos mecanismos adicionales: memoria celular y nichos celulares. Se invita a los oyentes a plantear dudas sobre estos conceptos hasta este punto.

Memoria Celular: Mantenimiento del Patrón Genético

Definición y Mecanismos

• La memoria celular se refiere al mecanismo mediante el cual las células mantienen patrones específicos de expresión génica a lo largo de generaciones celulares.

• Cambios epigenéticos son fundamentales; por ejemplo, modificaciones en los niveles de condensación cromatínica se heredan entre células progenitoras e hijas manteniendo activos conjuntos específicos de genes.

Identidad Celular

• La identidad celular (ejemplo: hepatocitos vs fibroblastos o neuronas) se preserva gracias a la expresión continua del mismo conjunto molecular (proteínas/ARN).

Cambios Epigenéticos Específicos

• Ejemplos incluyen metilación del ADN que persiste tras replicación; las células hijas conservan patrones similares a sus progenitoras sin alterar secuencias genéticas originales.

Circuitos de Retroalimentación

• Además de cambios epigenéticos, existen circuitos positivos donde una señal induce expresión génica que perpetúa dicha expresión mediante retroalimentación positiva. Por ejemplo:

Cellular Memory and Niches: Understanding Cell Differentiation

Cellular Independence and Positive Feedback Mechanisms

• Cells can become independent of external signals, continuing to express certain molecules due to positive feedback mechanisms. This phenomenon is crucial for cellular specification and determination.

• In cellular determination, a cell receives a signal that influences its identity; however, it retains this information even in the absence of the signal. This retention allows for sustained expression of specific proteins essential for maintaining cell type.

• The initial signaling can lead to differentiation processes where a specific cell type is formed, with characteristics preserved through positive feedback loops. These loops help maintain positional information within the organism.

• Positive feedback acts as a mechanism for cellular memory, enabling cells to retain their identity and contribute to stability within their respective tissues or systems.

Understanding Cellular Niches

Definition and Importance of Cellular Niches

• A "cellular niche" refers to specialized microenvironments that support specific types of cells, particularly stem cells. These niches are critical for maintaining the unique properties of stem cells during development and tissue maintenance.

Characteristics of Stem Cells

• Stem cells are undifferentiated cells capable of self-renewal and proliferation; they can divide symmetrically (producing two identical stem cells) or asymmetrically (yielding one stem cell and one differentiated cell). This versatility is vital for tissue regeneration.

• As stem cells proliferate towards specific fates, they lose some potentiality—transitioning from totipotent (capable of forming an entire organism) to multipotent (limited to certain lineages) states as differentiation progresses.

Role in Tissue Maintenance

• Stem cells play a significant role in maintaining tissues throughout embryonic development by continuously replenishing differentiated cell populations while preserving their own numbers through self-renewal capabilities.

Dynamics Within Cellular Niches

Components of Cellular Niches

• Cellular niches consist not only of the stem cells themselves but also include surrounding stromal cells, extracellular matrix components, soluble signaling molecules, and blood vessels—all contributing to the maintenance of stem cell properties.

Progenitor Cells vs Stem Cells

• Progenitor cells arise from asymmetric divisions of stem cells; they can proliferate but lack self-renewal capacity—leading them toward differentiation into specialized cell types while increasing overall cellular diversity within tissues.

Organization into Tissues

• Most multicellular organisms organize their numerous cell types into cooperative structures known as tissues which further aggregate into organs and systems—highlighting complex intercellular communication necessary for functional regulation despite ongoing cellular turnover.

This structured overview captures key concepts related to cellular memory mechanisms, niche environments supporting stem cell functionality, and the broader implications on tissue organization within multicellular organisms.

Introduction to Cellular Organization in Multicellular Organisms

Importance of Extracellular Matrix and Stem Cells

• The extracellular matrix (ECM) plays a crucial role in cellular memory and the maintenance of stem cells, which are vital for sustaining various tissues.

• Not all tissues rely on stem cells for maintenance; however, they are essential for many structures within multicellular organisms.

• The interaction between cells and the ECM is fundamental for tissue and organ maintenance, providing mechanical support as well as participating in communication processes among cells.

Overview of Upcoming Topics

• The session concludes with an invitation for questions, indicating a brief delay before proceeding to summarize key points discussed during the class.

• Next week’s focus will be on intracellular signaling—how cells communicate within tissues and across different organs, leading to intracellular responses.

Future Discussions on Cell Differentiation and Tumor Biology

• Future classes will cover cell differentiation mechanisms in multicellular organisms, revisiting concepts like cellular memory and positive feedback loops that influence this process.

• There will also be discussions on tumor biology, highlighting how neoplastic cell behavior mimics developmental molecular mechanisms but occurs uncontrollably.

Programmed Cell Death

• A significant topic will be programmed cell death (apoptosis), which is a normal part of development where cells actively die rather than just ceasing to function. This process is essential for maintaining homeostasis within tissues.

Review Sessions Before Exams