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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
Stem cell
progenetor cell
S
P
S
P
S
P
S
Symmetric division in mammalian cells
S
S
S
S
P
S
S
P
P
P
S
S
S
S
S
local environment
S
P
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 selfrenewal 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
Oligodendrocyte
haemapoietic stem cells
primodial germ cells
bone marrow
Hoechest-excluding bone marrow
bone marrow
bone marrow stroma
Hoechest-excluding muscle
unexpected derivatives
neurons
hepatocyte
all tissue type
muscle
muscle
hepatocyte
neuron and glia
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