scholarly journals Transcriptional networks are dynamically regulated during cell cycle progression in human Pluripotent Stem Cells

2020 ◽  
Author(s):  
Anna Osnato ◽  
Ludovic Vallier
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Model Systems ◽  
Transcriptional Networks ◽  
Reporter System ◽  
Cycle Progression ◽  
Sequence Of Events

AbstractCell cycle progression follows a precise sequence of events marked by different phases and check points which are associated with specific chromatin organisation. Whilst these changes have been extensively studied, their consequences on transcriptional networks remain to be fully uncovered, especially in dynamic model systems such as stem cells. Here, we take advantage of the FUCCI reporter system to show that chromatin accessibility, gene expression and key transcription factors binding change during cell cycle progression in human Embryonic Stem Cells (hESCs). These analyses reveal that core pluripotency factors such as OCT4, NANOG and SOX2 but also chromatin remodelers such as CTCF and RING1B bind the genome at specific phases of the cell cycle. Importantly, this binding pattern allows differentiation in the G1 phase while preserving pluripotency in the S/G2/M. Our results highlight the importance of studying transcriptional and epigenetic regulations in the dynamic context of the cell cycle.

scholarly journals Epigenetic regulations follow cell cycle progression during differentiation of human pluripotent stem cells

2020 ◽  
Author(s):  
Pedro Madrigal ◽  
Siim Pauklin ◽  
Kim Jee Goh ◽  
Rodrigo Grandy ◽  
Anna Osnato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Activator Protein 1 ◽  
Cellular Division ◽  
Mapk Signalling

AbstractMost mammalian stem cells undergo cellular division during their differentiation to produce daughter cells with a new cellular identity. However, the cascade of epigenetic events and molecular mechanisms occurring between successive cell divisions upon differentiation have not yet been described in detail due to technical limitations. Here, we address this question by taking advantage of the Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) reporter to develop a culture system allowing the differentiation of human Embryonic Stem Cells (hESCs) synchronised for their cell cycle. Using this approach, we have assessed the epigenome and transcriptome dynamics during the first two divisions leading to definitive endoderm. We first observed that transcription of key markers of differentiation occurs before division suggesting that differentiation is initiated during the progression of cell cycle. Furthermore, ATAC-seq shows a major decrease in chromatin accessibility after pluripotency exit indicating that the first event of differentiation is the inhibition of alternative cell fate. In addition, using digital genomic footprinting we identified novel cell cycle-specific transcription factors with regulatory potential in endoderm specification. Of particular interest, Activator protein 1 (AP-1) controlled p38/MAPK signalling seems to be necessary for blocking endoderm shifting cell fate toward mesoderm lineage. Finally, histone modifications analyses suggest a temporal order between different marks. We can also conclude that enhancers are dynamically and rapidly established / decommissioned between different cell cycle upon differentiation. Overall, these data not only reveal key the successive interplays between epigenetic modifications during differentiation but also provide a valuable resource to investigate novel mechanisms in germ layer specification.

scholarly journals Babam2 Regulates Cell Cycle Progression and Pluripotency in Mouse Embryonic Stem Cells as Revealed by Induced DNA Damage

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 397
Author(s):  
Cheuk Yiu Tenny Chung ◽  
Paulisally Hau Yi Lo ◽  
Kenneth Ka Ho Lee
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Gamma Irradiation ◽  
Cellular Senescence ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Cycle Progression ◽  
Cycle Regulation

BRISC and BRCA1-A complex member 2 (Babam2) plays an essential role in promoting cell cycle progression and preventing cellular senescence. Babam2-deficient fibroblasts show proliferation defect and premature senescence compared with their wild-type (WT) counterpart. Pluripotent mouse embryonic stem cells (mESCs) are known to have unlimited cell proliferation and self-renewal capability without entering cellular senescence. Therefore, studying the role of Babam2 in ESCs would enable us to understand the mechanism of Babam2 in cellular aging, cell cycle regulation, and pluripotency in ESCs. For this study, we generated Babam2 knockout (Babam2−/−) mESCs to investigate the function of Babam2 in mESCs. We demonstrated that the loss of Babam2 in mESCs leads to abnormal G1 phase retention in response to DNA damage induced by gamma irradiation or doxorubicin treatments. Key cell cycle regulators, CDC25A and CDK2, were found to be degraded in Babam2−/− mESCs following gamma irradiation. In addition, Babam2−/− mESCs expressed p53 strongly and significantly longer than in control mESCs, where p53 inhibited Nanog expression and G1/S cell cycle progression. The combined effects significantly reduced developmental pluripotency in Babam2−/− mESCs. In summary, Babam2 maintains cell cycle regulation and pluripotency in mESCs in response to induced DNA damage.

scholarly journals B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

PLoS ONE ◽  
2008 ◽  
Vol 3 (6) ◽  
pp. e2478 ◽  
Author(s):  
Kirill V. Tarasov ◽  
Yelena S. Tarasova ◽  
Wai Leong Tam ◽  
Daniel R. Riordon ◽  
Steven T. Elliott ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Cycle Progression ◽  
Chromosomal Stability ◽  
Normal Cell Cycle

scholarly journals BRPF3-HUWE1-mediated regulation of MYST2 is required for differentiation and cell-cycle progression in embryonic stem cells

2020 ◽  
Vol 27 (12) ◽  
pp. 3273-3288
Author(s):  
Hye In Cho ◽  
Min Seong Kim ◽  
Jina Lee ◽  
Byong Chul Yoo ◽  
Kyung Hee Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Development ◽  
Cell Cycle Progression ◽  
Histone Acetyltransferase ◽  
Embryoid Body ◽  
Embryonic Stem ◽  
Negative Regulator ◽  
Cycle Progression

AbstractBrpf-histone acetyltransferase (HAT) complexes have important roles in embryonic development and regulating differentiation in ESCs. Among Brpf family, Brpf3 is a scaffold protein of Myst2 histone acetyltransferase complex that plays crucial roles in gene regulation, DNA replication, development as well as maintaining pluripotency in embryonic stem cells (ESCs). However, its biological functions in ESCs are not elucidated. In this study, we find out that Brpf3 protein level is critical for Myst2 stability and E3 ligase Huwe1 functions as a novel negative regulator of Myst2 via ubiquitin-mediated degradation. Importantly, Brpf3 plays an antagonistic role in Huwe1-mediated degradation of Myst2, suggesting that protein–protein interaction between Brpf3 and Myst2 is required for retaining Myst2 stability. Further, Brpf3 overexpression causes the aberrant upregulation of Myst2 protein levels which in turn induces the dysregulated cell-cycle progression and also delay of early embryonic development processes such as embryoid-body formation and lineage commitment of mouse ESCs. The Brpf3 overexpression-induced phenotypes can be reverted by Huwe1 overexpression. Together, these results may provide novel insights into understanding the functions of Brpf3 in proper differentiation as well as cell-cycle progression of ESCs via regulation of Myst2 stability by obstructing Huwe1-mediated ubiquitination. In addition, we suggest that this is a useful report which sheds light on the function of an unknown gene in ESC field.

TRPV3 Channel Negatively Regulates Cell Cycle Progression and Safeguards the Pluripotency of Embryonic Stem Cells

2015 ◽  
Vol 231 (2) ◽  
pp. 403-413 ◽  
Author(s):  
Iek Chi Lo ◽  
Hing Chung Chan ◽  
Zenghua Qi ◽  
Kwun Lam Ng ◽  
Chun So ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Cycle Progression

scholarly journals G1-phase progression in pluripotent stem cells

2021 ◽  
Author(s):  
Menno ter Huurne ◽  
Hendrik G. Stunnenberg
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Cell Number ◽  
Molecular Networks ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Expression Of Genes ◽  
Promote Cell Cycle Progression

AbstractDuring early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are mechanistically intertwined. The picture that emerges from studies on the cell cycle of embryonic stem cells is one in which proteins that promote cell cycle progression prevent differentiation and vice versa. Here, we review which transcription factors and signalling pathways play a role in both maintenance of pluripotency as well as cell cycle progression. We will not only describe the mechanism behind their function but also discuss the role of these regulators in different states of mouse pluripotency. Finally, we elaborate on how canonical cell cycle regulators impact on the molecular networks that control the maintenance of pluripotency and lineage specification.

scholarly journals Direct observation of cell cycle progression in living mouse embryonic stem cells on an extracellular matrix of E-cadherin

SpringerPlus ◽  
2013 ◽  
Vol 2 (1) ◽  
pp. 585 ◽  
Author(s):  
Dragomirka Jovic ◽  
Asako Sakaue-Sawano ◽  
Takaya Abe ◽  
Chong-Su Cho ◽  
Masato Nagaoka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Extracellular Matrix ◽  
Embryonic Stem Cells ◽  
Direct Observation ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Cycle Progression ◽  
Living Mouse
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