Cell Differentiation I. Introduction: What is cell differentiation A. Terms 1.

Differentiation: process by which a cell acquires specialized structure and function needed for their distinct role in in organism a. Change I gene expression patterns resulting in observable changes in morphology and function b. Differentiated cells have distinct characteristics (biochemical, functional, morphological) c. Primary DNA sequence does not change with differentiation i. Control is at the level of which genes expressed and level of expression 2. State of differentiation degree of specialization, 3. Potency cells remaining differentiation potential a. Totipotent b. Pluripotent - cells that can proudce all 3 germlines, cant without assitance grow entire orgaism, cant direct themselves c. Multipotent - tissue specific stem cell, restricted to particular germ line d. Unipotent -only produce one type of cell over and over e. Terminally differentiated nonproliferative cells II. Regulation of cell differentiation A. Determination and how it is distinguished from differentiation 1. Determination: refers to the molecular mechanism and cues which commit a cell to particular lineage, regardless of any external sign of this commitment. a. Distinct from differentiation, which refers to morphological and functional alterations b. Refers to signals that specify cells eventual fate while differentiation is process of actually taking up that fate 2. Determination drives differentiation a. Expression of specific MRNA markers for cellular commitment to a specific lineage precedes appearance of function proteins or structural changes b. Cells can be genetically determined but morphologically undifferentiated c. Determination marker (gene expression changes) can drive functional differentiation B. How Is differentiation coordinated - acquisition and maintenance of cell differentiation requires extrinsic and intrinsic signals 1. Induction cells environment influences its differentiation behavior. a. Induction promotes development of organized tissues and organs with proper cells in proper place b. Mediators of inductive interactions i. Cell-cell interactions ii. Diffusible factors hormones, growth factors, cytokines iii. Cell-matrix interactions cytoskeleton c. Types of induction i. Instructive: occurs when definitive signal or interaction causes a cell to initiate new gene expression

 Different signals cause different effects If no signal, cell goes down default pathway ii. Permissive: responding cells are already committed to specific differentiation, but needs permissive setting If no permissive setting, cell remains undifferentiated d. Temporal specific of induction i. Timing of induction signal critical to induce intended differentiation pathway ii. Cell susceptible to abnormal differentiating along its default pathway 2. Epigenetic control =Refers to mechanism that lead to heritable phenotypes without changing DNA sequences a. Mechanisms silence or constitutively activate genes b. Epigenetic control provide a way to ensure similarly differentiated daughter cells have same characteristics c. Maintenance of cell differentiation involves stable environmental cues and autonomous epigenetic changes C. How flexible is differentiation 1. Determination and differentiation somewhat flexible when needed for health of the organ 2. Wound healing in intestinal tract a. Differentiated epithelial cells will shed their polarized morphology to close wound b. Regain polarized morphology III. Differentiation defects in humans A. Failure to develop particular differentiated cell types 1. X linked severe combined immune deficiency (X-SCID) a. Mutation inil2 gene which codes for a gamma chain shared by interleukins (secreted signaling protein which regulate immune cell function) b. Loss of interleukin signaling causes defect in lymphocyte differentiation lack T, B and NK cells B. Loss of differentiation within adult tissue 1. Cancer a. Anaplasia, dedifferentiation, plays role in development and behavior of tumors b. Failure or loss of differentiation contributes to carcinogenesis as most terminally differentiated cell types are not proliferative c. Treatment: force tumor to differentiate so it will not grow C. Transdifferentation: inappropriate acquisition of characteristics of a different tissue

Regenerative Medicine and stem cells

1.)

Generate a general understanding of what a stem cell is and how our understanding and practical use

of stem cell biology is fueling the vibrant field of regenerative medicine What is a stem cell:

-maintain, repair, and regenerate several organ systems -ex. Blood, gut epithelium, male germ-line -can be isolated from early mammalian embryo (Embryo Stem Cell/ESCs) or by cellular programming to give rise to any cell type Common definition: 1.) 2.) 3.) types 4.) Maintained within specialized tissue environment through genetic and epigenetic regulatory processes Undifferentiated but capable of giving rise to all cell types under appropriate conditions Can divide indefinitely Stem cell divisions maintain a balance between self-renewal and commitment to differentiated cell

Practical use of stem cell biology -play important role in cancer