Stem Cell Biology

Stem Cell The capacity of both self renewal and to generate differentiated progeny Byron Whites, US Supreme Court “ It’s hard to define, but I know when I see it.”

Properties of stem cells 1. asymmetric division S P S S P S P progenetor cell Stem cell

S S S P P S P P S S S S Symmetric division in mammalian cells

S S S SP local environment

2. Self -Renewal capacity allow the stem cell size to be regulated by factors that control the self-renewing or differentiation…. mammals ie. HSC : Haemopoietic Stem Cell murine does not have unlimited self- renewal potentials human self renewal is not for all life-span

3. Mitotic Quiescence Skin or bone marrow Stem cell  divdide slowly or rarely Drosophilla ovary or mammalian intestinal crypt stem cell  Divide every 12 hrs

4. Mother of all cells The ability to regenerate clonally the entire adult tissue from which they derive.

Control of self renewal  Extrinsic regulation of self renewal 1. The existence in a microenvironment which exclude the factors that cause differentiation 2. The proliferation of stem cell increase in response to tissue damage

Progenetor that have been found to exhibit unexpected development potentials progenitor unexpected derivatives Oligodendrocyte neurons haemapoietic stem cells hepatocyte primodial germ cells all tissue type bone marrow muscle Hoechest-excluding bone marrow muscle bone marrow hepatocyte bone marrow stroma neuron and glia Hoechest-excluding muscle blood cells Neurosphere blood cell Neurosphere muscle Neurosphere many somatic lineage Current biology vol 11 No 1

 Identity of factors that control stem cell renewal and their mechanism of action 1.GLP-1: notch releted receptors maintenance of Celegance germ-line stem cell mutation causes meiosis and differentiation 2. EGF promote adult proliferation of stem cell from adult CNS 3. b.EGF promote adult and embryonic stem cell proliferation 4. TGF-ß inhibit primodial germ cell and intestine crypt stem cell proliferation

Maintenance of uncommitted state by intrinsic factors  Maintain un committed nature of stem cell without influencing proliferation 1. Maternally inherited and distribute asymmetry to daughter cells 2. Repress the transcription of embryonic genes that cause commitment to particular somatic fate

Control of stem cell survival G0 G1 May be controlled by steel( stem cell factor): Promote survival of HSC and promodial germ cell but not proliferation

ikaros gene Zinc fingerprotein present in HSC Prevent development of multiple lymphoid derivatives SCL A transcriptional factormutation may prevent the development of haematopoietic derivatives

Stem cells 1. Adult stem cell ( somatic) differentiate into limited cell types 2. Embryonic stem cells( ES) contribute to all tissue types

Two basic properties of embryonic stem cells 1.Prolonged self renewal 2.Potentials to differentiate into one or more specialized cell type

Three types of pluoripotent cell type to date 1.Embryonic carcinoma( EC) a. derived from un differentiate stem cell of germ cell tumor b. may be differentiate to produce derivatives of all three germ layers in vitro or through tetracarcinoma formation

2. Human Embryonic Germ(EG )cells derived from primodial germ cells in the genital ridges of developing embryo( 5-9 weeks after fertilization) 3. Human Embryonic Stem( ES) cell derived from pre-implantation embryo, from ICM( inner Cell Mass) of human blastocysts, produced by in vitro fertilization

Establishment of Pluripotent ES cells using three different approach 1.Retransfer of ES cells into early embryo  give rise to somatic cells 2. Es cell differentiate to generate all three layers in vivo 3. ES pluripotency established during in vitro differentiation  differentiation of precursor cells into terminally differentiated somatic cells in vitro