SC cell cycle regulation and asymmetric cell division

SC cell cycle regulation and asymmetric cell division - SC...

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SC cell cycle regulation and asymmetric cell division Session X 4/5/06
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Cell division of an animal cell he mechanism of cell division - apter 18 The mechanism of cell division chapter 18 Alberts - Mol Bio of the Cell
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G0 phase
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ell c cle control in ESC roliferative Properties of ESC Cell cycle control in ESC Proliferative Properties of ESC Proliferate w/o apparent limit, not subject to ntact inhibition contact inhibition They can multiply w/o serum, can not enter a quiescence state or undergo senescence. Tumorigenic when transplanted to the body resemble neoplastic cells but without genetic lesions in protooncogenes and tumor suppressor genes
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Mouse ESCs lack control of G1 associated with Rb-E2F pathway
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ESCs display a very short G1 phase ~1.5 hours during which e hypophosphorylated G1 Rb is undetectable Rb is likely to the hypophosphorylated G1 Rb is undetectable. Rb is likely to be phosphorylated immediately after mitosis in ESCs.
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Are ESCs subject to G1 regulation by Rb? arly G1 cyclinD/cdk4 activity 1. Early G1 cyclinD/cdk4 activity Cyclin D1 and D3 are expressed at low levels in ESC; Cyclin D2 is not expressed in ESC; Induced differentiation leads to D- type cyclin expression d robust cdk4 activity; and robust cdk4 activity; Epiblast cells do not express appreciable D-type cyclin until astrulation commences gastrulation commences.
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2. Growth inhibition by p16 ink4a cyclinD-CDK4/6 is resistant to the growth inhibition activity of p16. Withdraw of LIF and subsequent differentiation is i d b iti ti t accompanied by sensitization to p16.
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3. Rb family genes knockout test Sage J et al., 2000
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Reduced differentiation T WT KO Dannenberg et al., 2000 Advanced neuronal (N) and muscle (M) differentiation in teratocarcinomas generated with wt ES cells. KO teratocarcinomas lack muscle differentiation and exist of primitive, relatively undifferentiated neuronal cells (PN) with rosette-like structures (R).
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Mouse ESCs lack control of G1 associated with Ras/ERK pathway or mitogen
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Disruption of Ras/ERK pathway doesn’t affect ECS proliferation but impaired endoderm differentiation. inner cell mass (ICM), trophectoderm (T) doderm lineages (visceral endoderm VE and parietal endoderm PE) endoderm lineages (visceral endoderm, VE, and parietal endoderm, PE) Similar results were obtained from SOS and SRF disruptions
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PI3K signalling contributes to ES cell cycle control
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SC depend PI3K activity for proliferation
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This note was uploaded on 09/28/2008 for the course BIO 4400 taught by Professor Tumbar,td during the Spring '07 term at Cornell University (Engineering School).

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SC cell cycle regulation and asymmetric cell division - SC...

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