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Series GSE137951 Query DataSets for GSE137951
Status Public on Sep 14, 2020
Title p53 activation during ribosome biogenesis regulates normal erythroid differentiation. [expression]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q- syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis shows that ribosome biogenesis is abruptly interrupted by the drop of rDNA transcription and the collapse of ribosomal protein neo-synthesis. Its premature arrest by RNA polI inhibitor, CX-5461 targets the proliferation of immature erythroblasts. We also show that p53 is activated spontaneously or in response to CX-5461 concomitantly to ribosome biogenesis arrest, and drives a transcriptional program in which genes involved in cell cycle arrest, negative regulation of apoptosis and DNA damage response were upregulated. RNA polI transcriptional stress results in nucleolar disruption and activation of ATR-CHK1-p53 pathway. Our results imply that the timing of ribosome biogenesis extinction and p53 activation are crucial for erythroid development. In ribosomopathies in which ribosome availability is altered by unbalanced production of ribosomal proteins, the threshold of ribosome biogenesis down-regulation could be prematurely reached and together with pathological p53 activation prevents a normal expansion of erythroid progenitors.
 
Overall design The purpose of the dataset is to profile analyze the effect of ribosome biogenesis in erythroblast cells
 
Contributor(s) Boussaid I, Fontenay M
Citation(s) 32818241
Submission date Sep 24, 2019
Last update date Sep 16, 2020
Contact name Ismael Boussaid
E-mail(s) boussaid.ismael@gmail.com
Phone +33618115659
Organization name Inserm
Lab Institut Cochin
Street address 22 Rue Mechain
City Paris
ZIP/Postal code 75014
Country France
 
Platforms (1)
GPL22936 [hta20_Hs_ENTREZG version 20] [HTA-2_0-st] GeneChip Human Transcriptome Array 2.0
Samples (22)
GSM4094902 erythroid cell obtained from CD34 culture - 48h - vehicle 01_CO6-CTL
GSM4094903 erythroid cell obtained from CD34 culture - 48h - CX-5461 02_CO6-CX
GSM4094904 erythroid cell obtained from CD34 culture - 48h - vehicle 03_CO26-CTL
This SubSeries is part of SuperSeries:
GSE157210 p53 activation during ribosome biogenesis regulates normal erythroid differentiation.
Relations
BioProject PRJNA573943

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
GSE137951_RAW.tar 605.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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