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Series GSE166027 Query DataSets for GSE166027
Status Public on Sep 15, 2021
Title rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin [scRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
 
Overall design Examination of gene expression in control and CX-5461 treated ES cells in single-cell level.
 
Contributor(s) Yu H, Sun Z
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Submission date Feb 02, 2021
Last update date Sep 15, 2021
Contact name Hua Yu
E-mail(s) huayu@zju.edu.cn
Phone 18758008246
Organization name Zhejiang University
Street address 866 Yuhangtang Rd
City Hangzhou
ZIP/Postal code 310058
Country China
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM5060414 Control_ES 1
GSM5060415 Control_ES 2
GSM5060416 Control_ES 3
This SubSeries is part of SuperSeries:
GSE166041 rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin
Relations
BioProject PRJNA699001
SRA SRP304374

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE166027_single_cell_gene_expression_CX5461.csv.gz 15.7 Mb (ftp)(http) CSV
GSE166027_single_cell_gene_expression_Control.csv.gz 10.4 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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