Cell Cycle Features of Primate Embryonic Stem Cells

Fluckiger, Anne Catherine; Marcy, Guillaume; Marchand, Mélanie; Nègre, Didier; Cosset, François‐Loïc; Mitalipov, Shoukhrat; Wolf, Don P.; Savatier, Pierre; Dehay, Colette

doi:10.1634/stemcells.2005-0194

Cited by 164 publications

(157 citation statements)

References 33 publications

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“…This pattern of expression of Cyclin E is not unique to nematodes. Cyclin E expression has been shown to be continuous throughout the cell cycle in germline stem cells of Drosophila (23) and embryonic stem (ES) cells from mouse (24) and primates (25). High level of cyclin E was proposed to indicate ''stemness'' of the cells (23).…”

Section: Discussionmentioning

confidence: 99%

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Grishok

Hoersch

Sharp

2008

Proc. Natl. Acad. Sci. U.S.A.

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In Caenorhabditis elegans , a vast number of endogenous short RNAs corresponding to thousands of genes have been discovered recently. This finding suggests that these short interfering RNAs (siRNAs) may contribute to regulation of many developmental and other signaling pathways in addition to silencing viruses and transposons. Here, we present a microarray analysis of gene expression in RNA interference (RNAi)-related mutants rde-4 , zfp-1 , and alg-1 and the retinoblastoma (Rb) mutant lin-35 . We found that a component of Dicer complex RDE-4 and a chromatin-related zinc finger protein ZFP-1, not implicated in endogenous RNAi, regulate overlapping sets of genes. Notably, genes a) up-regulated in the rde-4 and zfp-1 mutants and b) up-regulated in the lin-35 (Rb) mutant, but not the down-regulated genes are highly represented in the set of genes with corresponding endogenous siRNAs (endo-siRNAs). Our study suggests that endogenous siRNAs cooperate with chromatin factors, either C. elegans ortholog of acute lymphoblastic leukemia-1 (ALL-1)-fused gene from chromosome 10 (AF10), ZFP-1, or tumor suppressor Rb, to regulate overlapping sets of genes and predicts a large role for RNAi-based chromatin silencing in control of gene expression in C. elegans .

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Section: Discussionmentioning

confidence: 99%

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Grishok

Hoersch

Sharp

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…One of the explanations for the high aneuploidy rate in hESCs cells, compared with hiPSCs and controls, might lies in the possibility that ESCs guarantee rapid cell division by bypassing certain mechanisms of cell-cycle control and by that, enabling the survival of chromosomally aberrant cells. As it turns out, in early development, the strict requirements for cell growth are suspended to allow rapid cell proliferation 38,39 and is activated again when ESCs are induced to differentiate into embryoid bodies. 40,41 A recent study, conducted by Mayshar et al 34 , identified a substantial number of hiPS cell lines carrying full and partial chromosomal aberrations.…”

Section: Aneuploidy Screeningmentioning

confidence: 99%

Screening of human pluripotent stem cells using CGH and FISH reveals low-grade mosaic aneuploidy and a recurrent amplification of chromosome 1q

et al. 2012

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Pluripotency and proliferative capacity of human embryonic stem cells (hESCs) make them a promising source for basic and applied research as well as in therapeutic medicine. The introduction of human induced pluripotent cells (hiPSCs) holds great promise for patient-tailored regenerative medicine therapies. However, for hESCs and hiPSCs to be applied for therapeutic purposes, long-term genomic stability in culture must be maintained. Until recently, G-banding analysis was considered as the default approach for detecting chromosomal abnormalities in stem cells. Our goal in this study was to apply fluorescence in-situ hybridization (FISH) and comparative genomic hybridization (CGH) for the screening of pluripotent stem cells, which will enable us identifying chromosomal abnormalities in stem cells genome with a better resolution. We studied three hESC lines and two hiPSC lines over long-term culture. Aneuploidy rates were evaluated at different passages, using FISH probes (12,13,16,17,18,21,X,Y). Genomic integrity was shown to be maintained at early passages of hESCs and hiPSCs but, at late passages, we observed low rates mosaiciam in hESCs, which implies a direct correlation between number of passages and increased aneuploidy rate. In addition, CGH analysis revealed a recurrent genomic instability, involving the gain of chromosome 1q. This finding was detected in two unrelated cell lines of different origin and implies that gains of chromosome 1q may endow a clonal advantage in culture. These findings, which could only partially be detected by conventional cytogenetic methods, emphasize the importance of using molecular cytogenetic methods for tracking genomic instability in stem cells.

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“…Although the short G1 and extended S-phase are also observed in murine, nonprimate, and primate ESC [6,7], the G1 to S transition seems to be subject to species-specific regulation [5].…”

Section: Introductionmentioning

confidence: 97%

An Important Role for CDK2 in G1 to S Checkpoint Activation and DNA Damage Response in Human Embryonic Stem Cells

et al. 2011

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A precise understanding of mechanisms used by human embryonic stem cells (hESCs) to maintain genomic integrity is very important for their potential clinical applications. The G1 checkpoint serves to protect genomic integrity and prevents cells with damaged DNA from entering S-phase. Previously, we have shown that downregulation of cyclindependent kinase 2 (CDK2) in hESC causes G1 arrest, loss of pluripotency, upregulation of cell cycle inhibitors p21 and p27 and differentiation toward extraembryonic lineages. In this study, we investigate in detail the role of CDK2 in cellular processes, which are crucial to the maintenance of genomic stability in hESC such as G1 checkpoint activation, DNA repair, and apoptosis. Our results suggest that downregulation of CDK2 triggers the G1 checkpoint through the activation of the ATM-CHK2-p53-p21 pathway. Downregulation of CDK2 is able to induce sustained DNA damage and to elicit the DNA damage response (DDR) as evidenced by the formation of distinct c-H2.AX and RAD52-BRCA1 foci in hESC nuclei. CDK2 downregulation causes high apoptosis at the early time points; however, this is gradually decreased overtime as the DDR is initiated. Our mass spectrometry analysis suggest that CDK2 does interact with a large number of proteins that are involved in key cellular processes such as DNA replication, cell cycle progression, DNA repair, chromatin modeling, thus, suggesting a crucial role for CDK2 in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in hESC. STEM CELLS 2011;29:651-659 Disclosure of potential conflicts of interest is found at the end of this article.

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Cell Cycle Features of Primate Embryonic Stem Cells

Cited by 164 publications

References 33 publications

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans

Screening of human pluripotent stem cells using CGH and FISH reveals low-grade mosaic aneuploidy and a recurrent amplification of chromosome 1q

An Important Role for CDK2 in G1 to S Checkpoint Activation and DNA Damage Response in Human Embryonic Stem Cells

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