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Series GSE129631 Query DataSets for GSE129631
Status Public on Jun 28, 2021
Title Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5−/− HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence.
Overall design Single-cell RNA sequencing was performed on HSCs from Mda5+/+ (IFIH1WT) and Mda5-/- (IFIH1KO) mice.
Contributor(s) Clapes T, Polyzou A, Sagar -, Gruen D, Trompouki E
Citation(s) 34253898
Submission date Apr 11, 2019
Last update date Oct 27, 2021
Contact name Sagar -
Organization name University Medical Center Freiburg
Department Department of Internal Medicine II
Lab Sagar
Street address Hugstetter Straße 55
City Freiburg
ZIP/Postal code 79106
Country Germany
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (24)
GSM3717643 IFIH1WT_P1_1
GSM3717644 IFIH1WT_P1_2
GSM3717645 IFIH1WT_P1_3
BioProject PRJNA532340
SRA SRP191994

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE129631_RAW.tar 8.3 Mb (http)(custom) TAR (of CSV)
GSE129631_celseq_barcodes.192.txt.gz 910 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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