Self‐renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase

  title={Self‐renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase},
  author={Klaus A. Becker and Prachi N Ghule and Jaclyn A. Therrien and Jane B. Lian and Janet L. Stein and Andre J. van Wijnen and Gary S. Stein},
  journal={Journal of Cellular Physiology},
Competency for self‐renewal of human embryonic stem (ES) cells is linked to pluripotency. However, there is a critical paucity of fundamental parameters of human ES cell division. In this study we show that human ES cells (H1 and H9; NIH‐designated WA01 and WA09) rapidly proliferate due to a very short overall cell cycle (15–16 h) compared to somatic cells (e.g., normal diploid IMR90 fibroblasts and NT‐2 teratocarcinoma cells). The human ES cell cycle maintains the four canonical cell cycle… 

Reprogramming the pluripotent cell cycle: Restoration of an abbreviated G1 phase in human induced pluripotent stem (iPS) cells

It is shown that reprogrammed iPS cells have cell cycle kinetics and dynamic subnuclear organization of regulatory machinery that are principal properties of pluripotent hES cells, and this support the concept that the abbreviated cell cycle of hES andiPS cells is functionally linked to pluripotency.

Human embryonic stem cells are pre‐mitotically committed to self‐renewal and acquire a lengthened G1 phase upon lineage programming

It is concluded that short‐term self‐renewal of pluripotent hES cells occurs autonomously, in part due to secreted factors, and that pluripotency is functionally linked to the abbreviated hES cell cycle.

Lengthened G1 phase indicates differentiation status in human embryonic stem cells.

This work coexpressed the chromatin-decorating H2B-GFP fusion protein and the fluorescence ubiquitination cell cycle indicator (FUCCI)-G1 fusion protein, a G1 phase-specific reporter, in hESCs to measure the cell cycle status in live cells, and found that FUCCI-G1 expression is weakly detected in undifferentiated h ESCs, but rapidly increases upon differentiation.

Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation

C cultured undifferentiated hESCs are capable of preventing entry into S‐phase by activating the G1/S checkpoint upon damage to their genetic complement.

JMJD5 Regulates Cell Cycle and Pluripotency in Human Embryonic Stem Cells

Genetic and biochemical evidence is provided that the JMJD5/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in hESCs.

Lineage‐Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause

A novel G2 cell cycle pause that is required for endodermal differentiation is identified and important new mechanistic insights into early events of lineage commitment are provided.

The brevity of G1 is an intrinsic determinant of naïve pluripotency

A model in which LIF signalling stimulates the G1 to S phase transition to shield mESCs from undesired differentiation signals and help them to self-renew in the pluripotent state is proposed.

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS DNA Damage Mediated S and G2 Checkpoints in Human Embryonal Carcinoma Cells

Investigation of ionizing radiation (IR)-mediated cell cycle checkpoints in undifferentiated and retinoic acid-differentiated human embryonal carcinoma (EC) cells found IR-mediated phosphorylation of ataxia-telangiectasia mutated, (CHK1), and checkpoint kinase 2 were distinctly higher in Undifferentiated EC cells compared with differentiated EC cells.

The abbreviated pluripotent cell cycle

For the first time, unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency are considered.



Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture.

The clonal derivation of two human ES cell lines, H9.1 and H.2, demonstrates the pluripotency of single human ES cells, the maintenance of pluripOTency during an extended period of culture, and the long-term self-renewing properties of cultured human ES Cells.

Cell cycle control of embryonic stem cells

The unique cell cycle structure and mechanism of cell cycle control indicates that the cell cycle machinery plays a role in establishment or maintenance of the stem cell state, supported by the frequent involvement ofcell cycle regulatory molecules in cell immortalization.

Cell Cycle Features of Primate Embryonic Stem Cells

Using flow cytometry measurements combined with quantitative analysis of cell cycle kinetics, we show that rhesus monkey embryonic stem cells (ESCs) are characterized by an extremely rapid transit

Derivation, growth and applications of human embryonic stem cells.

Recent progress in the derivation and growth of undifferentiated hES cells and their differentiated progeny, and the problems associated with these techniques are summarised.

Pluripotent cell division cycles are driven by ectopic Cdk2, cyclin A/E and E2F activities

The results show that rapid cell division cycles in primitive cells of embryonic origin are driven by extreme levels of Cdk activity that lack normal cell cycle periodicity.

Comparative transcriptional profiling of two human embryonic stem cell lines

A stringent direct comparison between data sets obtained from two human ESCs are reported in order to obtain a list of genes that are enriched in ESCs and this work found 133 genes overlapped between the three pluripotent populations.

Contrasting patterns of retinoblastoma protein expression in mouse embryonic stem cells and embryonic fibroblasts.

Absence of hypophosphorylated RB and cell cycle-dependent change in total RB protein level may be relevant to the high proliferation rate and to the tumorigenic nature of mouse embryonic stem cells.

Gene expression in human embryonic stem cell lines: unique molecular signature.

The first detailed characterization of undifferentiated huES cells is presented and several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome.

Embryonic stem cell lines derived from human blastocysts.

Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate

Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell differentiation.

The data support that hESC may be capable of differentiation into germ cells although further confirmation is needed, and it is suggested that strategies such as stepwise adaptation will be needed before implementing a serum-free culture condition for h ESC lines that have previously been derived in a medium containing serum.