stem cell biology. stem cell the capacity of both self renewal and to generate differentiated...
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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
SP
S
SP
SP
progenetor cell
Stem cell
SS
S
PP
S
PP
S
SS
S
Symmetric division in mammalian cells
SS
S
S P
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
