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Series GSE166025 Query DataSets for GSE166025
Status Public on Sep 15, 2021
Title rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin [RNA-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 and mouse embryo.
Contributor(s) Yu H, Sun Z
Citation(s) 34753899
Submission date Feb 02, 2021
Last update date Nov 30, 2021
Contact name Hua Yu
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 (12)
GSM5060376 ES Control_1
GSM5060377 ES Control_2
GSM5060378 ES CX-5461_1
This SubSeries is part of SuperSeries:
GSE166041 rRNA Biogenesis Regulates Mouse 2C-like State by 3D Structure Reorganization of Peri-Nucleolar Heterochromatin
BioProject PRJNA698998
SRA SRP304372

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
GSE166025_gene_TPM_ES.xlsx 4.1 Mb (ftp)(http) XLSX
GSE166025_gene_TPM_Embryo.xlsx 2.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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