scholarly journals A transcriptional roadmap for 2C-like–to–pluripotent state transition

2020 ◽  
Vol 6 (22) ◽  
pp. eaay5181 ◽  
Author(s):  
Xudong Fu ◽  
Mohamed Nadhir Djekidel ◽  
Yi Zhang
Keyword(s):  
Intermediate State ◽  
State Transition ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Small Cell ◽  
Molecular Event ◽  
Cell Stage ◽  
Pluripotent State ◽  
Transcriptional Dynamics ◽  
The One

In mouse embryonic stem cell (ESC), a small cell population displays totipotent features by expressing a set of genes that are transiently active in 2-cell–stage embryos. These 2-cell–like (2C-like) cells spontaneously transit back into the pluripotent state. We previously dissected the transcriptional dynamics of the transition from pluripotency to the totipotent 2C-like state and identified factors that modulate the process. However, how 2C-like cells transit back into the pluripotent state remains largely unknown. In this study, we analyzed the transcriptional dynamics from the 2C-like state to pluripotent ESCs and identified an intermediate state. The intermediate state characterized by two-wave step up-regulation of pluripotent genes is different from the one observed during the 2C-like entry transition. Nonsense-mediated Dux mRNA decay plays an important role in the 2C-like state exit. Thus, our study not only provides a transcriptional roadmap for 2C-like–to–pluripotent state transition but also reveals a key molecular event driving the transition.

scholarly journals A dual reporter system identifies an intermediate state and sequential regulators of 2-cell-like-to-pluripotent state transition

2021 ◽  
Author(s):  
Chao Zhang ◽  
Jing Hao ◽  
Ming Shi ◽  
Yu-Xuan Li ◽  
Wang Yao ◽  
...  
Keyword(s):  
Intermediate State ◽  
Molecular Mechanisms ◽  
State Transition ◽  
Embryonic Stem ◽  
Dual Function ◽  
Reporter System ◽  
Cell Stage ◽  
Pluripotent State ◽  
Dual Reporter ◽  
Essential Transcription Factor

Mouse embryonic stem cells (ESCs) cycle in and out of 2-cell-like (2C-like) state in culture. The molecular mechanism governing the exit of 2C-like state remains obscure, partly due to the lack of a reporter system that can genetically mark intermediate states during exiting process. Here, we identify an intermediate state that is marked by the co-expression of MERVL::tdTomato and OCT4-GFP (MERLOT) during 2C-like-to-pluripotent state transition (2CLPT). Transcriptome and epigenome analyses demonstrate that MERLOT cells cluster closely with 8-16 cell stage mouse embryos, suggesting that 2CLPT partly mimics early preimplantation development. Through a CRISPRa screen, we identify an ARRDC3-NEDD4-OCT4 regulatory axis that plays an essential role in controlling 2CLPT. Furthermore, re-evaluating previously reported 2C-like state regulators reveals dual function of Chaf1a in regulating the entry and exit of 2C-like state. Finally, ATAC-Seq footprinting analysis uncovers Klf3 as an essential transcription factor required for efficient 2CLPT. Together, our study identifies a genetically traceable intermediate state during 2CLPT and provides a valuable tool to study molecular mechanisms regulating this process.

scholarly journals Transcription Factor Lbx1 Expression in Mouse Embryonic Stem Cell-Derived Phenotypes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stefanie Schmitteckert ◽  
Cornelia Ziegler ◽  
Liane Kartes ◽  
Alexandra Rolletschek
Keyword(s):  
Transcription Factor ◽  
Developmental Stages ◽  
Troponin T ◽  
Es Cells ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Cardiac Cells ◽  
Cell Stage

Transcription factor Lbx1 is known to play a role in the migration of muscle progenitor cells in limb buds and also in neuronal determination processes. In addition, involvement of Lbx1 in cardiac neural crest-related cardiogenesis was postulated. Here, we used mouse embryonic stem (ES) cells which have the capacity to develop into cells of all three primary germ layers. Duringin vitrodifferentiation, ES cells recapitulate cellular developmental processes and gene expression patterns of early embryogenesis. Transcript analysis revealed a significant upregulation ofLbx1at the progenitor cell stage. Immunofluorescence staining confirmed the expression of Lbx1 in skeletal muscle cell progenitors and GABAergic neurons. To verify the presence of Lbx1 in cardiac cells, triple immunocytochemistry of ES cell-derived cardiomyocytes and a quantification assay were performed at different developmental stages. Colabeling of Lbx1 and cardiac specific markers troponin T, α-actinin, GATA4, and Nkx2.5 suggested a potential role in early myocardial development.

scholarly journals Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition

Cell Reports ◽  
2018 ◽  
Vol 22 (10) ◽  
pp. 2615-2627 ◽  
Author(s):  
Clara Lopes Novo ◽  
Biola-Maria Javierre ◽  
Jonathan Cairns ◽  
Anne Segonds-Pichon ◽  
Steven W. Wingett ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Long Range ◽  
State Transition ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Pluripotent State

scholarly journals A defined glycosylation regulatory network modulates total glycome dynamics during pluripotency state transition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Federico Pecori ◽  
Ikuko Yokota ◽  
Hisatoshi Hanamatsu ◽  
Taichi Miura ◽  
Chika Ogura ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
State Transition ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Developmentally Regulated ◽  
Polycomb Repressive Complex 2 ◽  
Pluripotent State ◽  
Lineage Decision ◽  
Early Mouse

AbstractEmbryonic stem cells (ESCs) and epiblast-like cells (EpiLCs) recapitulate in vitro the epiblast first cell lineage decision, allowing characterization of the molecular mechanisms underlying pluripotent state transition. Here, we performed a comprehensive and comparative analysis of total glycomes of mouse ESCs and EpiLCs, revealing that overall glycosylation undergoes dramatic changes from early stages of development. Remarkably, we showed for the first time the presence of a developmentally regulated network orchestrating glycosylation changes and identified polycomb repressive complex 2 (PRC2) as a key component involved in this process. Collectively, our findings provide novel insights into the naïve-to-primed pluripotent state transition and advance the understanding of glycosylation complex regulation during early mouse embryonic development.

scholarly journals Transient DUX4 expression induces blastomere-like expression program that is marked by SLC34A2

2021 ◽  
Author(s):  
Masahito Yoshihara ◽  
Ida Kirjanov ◽  
Sonja Nykänen ◽  
Joonas Sokka ◽  
Jere Weltner ◽  
...  
Keyword(s):  
Human Embryo ◽  
Embryonic Stem ◽  
Cell Stage ◽  
Cellular Models ◽  
Transcriptional Dynamics ◽  
Embryonic Genome ◽  
Experimental Approaches ◽  
Genome Activation ◽  
Expression Program

AbstractDUX4 has recently been recognized as a key regulator in human embryonic genome activation (EGA). The exact role of DUX4 in human embryo is still elusive, partly due to the cytotoxicity of persistent DUX4 expression in cellular models. We report here that a transient DUX4 expression in human embryonic stem cells (hESCs) retains cell viability while inducing an EGA-like expression program in a subpopulation of the cells. These cells showed resemblance to 8-cell stage blastomeres and were thus named induced blastomere-like (iBM) cells. Trajectory inference from the single-cell RNA-seq data suggested that the expression profile of these cells progressed in a manner similar to the morula to blastocyst transition in human embryo. Finally, viable iBM cells could be enriched using an antibody against NaPi2b (SLC34A2), paving the way for further experimental approaches. The iBM cells can become a powerful tool to model transcriptional dynamics and regulation during early human embryogenesis.

microRNA regulation of pluripotent state transition

2020 ◽  
Vol 64 (6) ◽  
pp. 947-954 ◽  
Author(s):  
Shao-Hua Wang ◽  
Chao Zhang ◽  
Yangming Wang
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Embryo Development ◽  
State Transition ◽  
Embryonic Stem ◽  
Short Review ◽  
Early Embryo ◽  
Mammalian Development ◽  
Early Embryo Development ◽  
Pluripotent State

Abstract microRNAs (miRNAs) play essential roles in mouse embryonic stem cells (ESCs) and early embryo development. The exact mechanism by which miRNAs regulate cell fate transition during embryo development is still not clear. Recent studies have identified and captured various pluripotent stem cells (PSCs) that share similar characteristics with cells from different stages of pre- and post-implantation embryos. These PSCs provide valuable models to understand miRNA functions in early mammalian development. In this short review, we will summarize recent work towards understanding the function and mechanism of miRNAs in regulating the transition or conversion between different pluripotent states. In addition, we will highlight unresolved questions and key future directions related to miRNAs in pluripotent state transition. Studies in these areas will further our understanding of miRNA functions in early embryo development, and may lead to practical means to control human PSCs for clinical applications in regenerative medicine.

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