Crosstalk between stem cell and cell cycle machineries

Kareta, Michael S.; Sage, Julien; Wernig, Marius

doi:10.1016/j.ceb.2015.10.001

Cited by 37 publications

(39 citation statements)

References 71 publications

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“…It has long been known that the durations of these phases can vary considerably across cell types (Dawson et al, 1965). For example, stem cells and immune cells have relatively brief G1 durations compared to somatic cells (Becker et al, 2006;Kareta et al, 2015;Kinjyo et al, 2015). Phase durations can also change under certain environmental stresses such as starvation, which lengthens G1 (Cooper, 2003), or DNA damage, which mainly prolongs G1 and G2 (Arora et al, 2017;Chao et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Evidence that the human cell cycle is a series of uncoupled, memoryless phases

Chao

Fakhreddin

Shimerov

et al. 2019

Molecular Systems Biology

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The cell cycle is canonically described as a series of four consecutive phases: G1, S, G2, and M. In single cells, the duration of each phase varies, but the quantitative laws that govern phase durations are not well understood. Using time‐lapse microscopy, we found that each phase duration follows an Erlang distribution and is statistically independent from other phases. We challenged this observation by perturbing phase durations through oncogene activation, inhibition of DNA synthesis, reduced temperature, and DNA damage. Despite large changes in durations in cell populations, phase durations remained uncoupled in individual cells. These results suggested that the independence of phase durations may arise from a large number of molecular factors that each exerts a minor influence on the rate of cell cycle progression. We tested this model by experimentally forcing phase coupling through inhibition of cyclin‐dependent kinase 2 ( CDK 2) or overexpression of cyclin D. Our work provides an explanation for the historical observation that phase durations are both inherited and independent and suggests how cell cycle progression may be altered in disease states.

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Section: Introductionmentioning

confidence: 99%

Evidence that the human cell cycle is a series of uncoupled, memoryless phases

Chao

Fakhreddin

Shimerov

et al. 2019

Molecular Systems Biology

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“…Cell fate switches correlation with cell cycle transition in dividing cells, whereas terminal differentiation is frequently associated with cell cycle exit. It is reported that the rapid cell division supports the selfrenewal of hESCs because of the shortened G1 cell cycle [14]. Cell cycle length and rate are determining factors for both self-renewal and differentiation of stem cells, so cell cycle analyses have value to determine the differentiation progress of hPSCs [15].…”

Section: The Cell Cycle Changes Of Hpscs During Osteogenic Differentimentioning

confidence: 99%

Establish deeper understanding on the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detail analyses

Zhou

Shi

Song³

et al. 2020

Preprint

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Background: Derivation of the osteoblast-like cell from human pluripotent stem cell becomes a hot topic in bone tissue engineering. Although many improvements have been achieved in this field, low induction efficiency because of the non-directed differentiation process hampers their application in bone regeneration. We think lack of detailed understanding on the osteogenic differentiation process should be the main reason.Methods: Monolayer cultured human embryonic stem cells and human induced pluripotent stem cells were inducted in traditional serum-containing osteogenic medium for 35 days. Except for traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied cell counting, cell telomerase activity, cell cycle and quantitative expression of runt-related transcription factor 2 as essential indicators to analyze the cell type changes during the differentiation process. Results: The population of differentiated cells are quite heterogenous throughout 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type changes and tumorigenicity of obtained cells. Moreover, nuclear staining should be a recommended method to evaluate the cell number, because, it is still a great challenge to dissociate cells with varying differentiation times into single cells with high survival rate. Finally, a dynamic map was made to integrated analysis of these results, and the cell types at defined stages of osteogenic differentiation of human pluripotent stem cells was concluded. Conclusions: This study lay foundation to improve the in vitro osteogenic differentiation efficiency of human pluripotent stem cells by supplementing functional compounds at each stage according to a time-frame, then establish a step-wised induction system in the future.

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“…In multicellular animals, only a handful of genes have been identified to play a central role in both cell cycle control and establishment of developmental processes. Recent studies provide evidence on the links between cell cycle and development, and emphasize the role of Geminin on fate commitment programs in stem and progenitor cells .…”

Section: Geminin a Regulator Of Lineage Specificationmentioning

confidence: 99%

Concise Review: Geminin—A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells

et al. 2016

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Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells. In embryonic as well as somatic stem cells, Geminin has been shown to interact with transcription factors and epigenetic regulators to drive gene expression programs and ultimately guide cell fate decisions. An ever-growing number of studies suggests that these interactions of Geminin and proteins regulating transcription are conserved among metazoans. Interactions between Geminin and proteins modifying the epigenome, such as members of the repressive Polycomb group and the SWI/SNF proteins of the permissive Trithorax, have long been established. The complexity of these interactions, however, is only just beginning to unravel, revealing key roles on maintaining stem cell self-renewal and fate specification. In this review, we summarize current knowledge and give new perspectives for the role of Geminin on transcriptional and epigenetic regulation, alongside with its regulatory activity in DNA replication and their implication in the regulation of stem and progenitor cell biology. STEM CELLS 2017;35:299-310 SIGNIFICANCE STATEMENTThe review focuses on the roles of Geminin in embryonic and somatic stem cells. More specifically, we have addressed how Geminin, through its regulatory roles in transcriptional and epigenetic control, impacts stem cell self-renewal versus differentiation decisions. In recent years, we and other researchers have studied extensively the transcriptional programs affected by Geminin in various developmental stages and tissues using murine models. However, what we wish to emphasize in this review-as well as to summarize findings in order to aid future studies-is the network of proteins that Geminin associates with at the epigenomic level. These interactions are critical for cellular pluri/multi-potency and differentiation decisions of stem and progenitor cells for maintenance of homeostasis. Last, but not least, we provide links between the transcriptional/epigenetic roles of Geminin and its more traditional role as a regulator of DNA replication. We believe that these two otherwise distinct roles of this protein are interconnected and we anticipate that our views will stimulate future studies with cutting edge research investing into how Geminin could be fine-tuned to assist tissue engineering in medical applications.

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Crosstalk between stem cell and cell cycle machineries

Cited by 37 publications

References 71 publications

Evidence that the human cell cycle is a series of uncoupled, memoryless phases

Evidence that the human cell cycle is a series of uncoupled, memoryless phases

Establish deeper understanding on the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detail analyses

Concise Review: Geminin—A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells

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