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35 Cards in this Set
- Front
- Back
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stem cell defining properties
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self-renewal:
divide and give rise to identical daughter cells with exactly the same properties as their immediate progenitor potency: -varying degrees (totipotent, pluripotent, multipotent) is the capacity to produce progeny of more than 1 functional cell type - distinguishes between stem cells - distinguishes from unipotent prgenitor cells |
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embryonic stem cells
where do they come from? |
develop from the totipotent fertilised egg
* ES cells are NOT totipotent => originate from cell type formed later in development (from epiblast) |
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Epiblast gives rise to
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the fetus
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trophoblast gives rise
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to the placenta
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hypoblast gives rise to
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the yolk sac
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The Epiblast
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epiblast cells are pluripotent=> capacity to give rise to cells of all three germ layers
- gives rise to germ cells - gives rise to tumours when ectopically transplanted teratocarcinomas - where ES cells come from |
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Leroy Stevens
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studied effects of pluripotent cell transplant to permitting sites=> development of teratocarcinomas, which showd differentiated cells types from all three germ layers
can be serially passaged by transplantation remain less differentiated when transplanted to peritoneal cavity |
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Barry Pierce
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embryoid bodies passaged in peritoneal cavity was used a teratocarcinoma source enriched in undifferentiated cells
- single cells can self-renew and generate multidifferentiated tumours upon transplantation to new animal host ==> teratocarcinomas have a clonal stem cell source (basis for Cancer stem cells idea) |
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can be transplanted into blastocoel cavity
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chaotic behaviour of EC can be brought under control
by the appropriate embryonic environment |
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ES cell can be obtained directly from the early embryo
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in the appropriate growth conditions, can be allowed to propagate
-can self renew - can produce all 3 germ layers |
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pluripotency
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capacity to give rise to derivatives of all three germ layers
normally only ICM can but so can ES, EC, EG and iPS cell lines |
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extrinsic regulation
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fibroblast feeder cells can maintain ES cells undiferentiated
can be replaced by Leukaemia Inhibitory Factor (LIF) LIF enables self renewal by activating STAT3 serum also required=> provides signal that prevents neural differentiation (contains BMPs) BMP prevents neural diff. => together with LIF prevent diff |
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BMP
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bone morphogenetic protein i
-> induces Inhibitor of differentiation -> negative HLH factors (sequester E proteins and block pro-neural activity of bHLH transcription factors |
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Establishment and maintenance of neural stem cells
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NS cells are multipotent
maintained by EGF and FGF-2 |
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where do NS cells come from?
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neuroepithelium -> radial glia -> adult SVZ astrocyte
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Primordial germ cells
where do they come from |
set aside from early post implantation epiblast at ~E6.5
- expand in number and migrate through hindgut arrive in genital ridges at ~E10.5 - give rise to male and female germ cells |
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are PGMs stem cells?
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NO- they are unipotent
but potency can be altered |
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haematopoietic stem cells
where do they come from? |
site of origin changes during mammalian development
-> in adults found in the bone marrow |
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what can haematopoietic stem cells do?
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can restore haematopoietic compartment in lethally irradiated mice
LT-HSCs can self renew => multipotent -> form CFU-S in spleen (clonal assay that measures stem cell content in haematopoietic tissue) Individual CFU-S derive from single cells |
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Skin stem cell therapy
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skin stem cells found between dermis and epidermis
- done when there's not enough skin left for grafts - no sweat glands/ hair ongoing research |
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stem cells may be used for patients:
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parkinsons
multiple sclerosis diabetes |
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medical attributes of stem cells
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genetically normal cells
unlimited multiplication unlimited differentiation |
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what must be know for implementing plutripotent cells
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what factors direct self renewal
what factors influence differentiation how to make normal cells in vitro -> how to reproduce normal differentiation pathways in vitro |
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mES cells culture conditions
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LIF and BMP
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hES cells culture conditions
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FGF2 + TGFbeta/activin
human embryonic stem cells |
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mEpiSCs
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FGF2 + TGFbeta/activin
transient cells derived by placing ES in EpiSC culture -> can make germ cells (unlike epi SC) |
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Mouse EpiSCs
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derived from epiblast of post implantation mouse embryo
-form teratocarcinome => pluripotent |
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effects of Nanog on expression
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Nanog is required together with Oct4 for sustaining the ES cell identity. present in hES cells and mES cells, absent from differentiated
Nanog acts in parallel with Stat3 to drive self renewal * overexpression of Nanog via a transgene construct is sufficient for driving self renewal bypassing Stat3 |
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Oct4
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-POU homeodomain transcription factor
-found only in pluripotent cells and germ cells -essential for specification of pluripotency in the ICM - often acts together with Sox2 - |
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Self-renewing endodermal progenitor lines from human ES and iPS
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unlimitted expansion
non-tumourigenic can be differentiated into glucose-responsive pancreatic beta-cells (diabetes treatemnt) |
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homogenous differentiation
cell transplant rejection |
r
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pluripotent remodelling
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metaphase II oocyte=> remove metaphase plate => fuse with fibroblast + activate => 10% form blastocyst => 10% develop into offspring
HOW? factors in the cytoplasm impose an oocyte specific transcription factor profile one the fibroblast genome |
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ntES cells
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nuclear transfer ES cells
-> can be derived this away -> can give specific stem cell type with specific differentiation protocols -> can provide models for human diseases |
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Potential
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bypass histocompatibility concerns
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Corneal burns
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cured by limbal stem cell transplantation
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