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Series GSE183497 Query DataSets for GSE183497
Status Public on Jan 25, 2022
Title In vivo CRISPR screening reveals druggable regulators of mammalian tissue regeneration [H2-ATAC-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Identifying new pathways that regulate mammalian regeneration is challenging due to the paucity of in vivo screening approaches. We employed pooled CRISPR knockout and activation screening in the regenerating liver to evaluate 164 chromatin regulatory proteins. Both screens identified imitation-SWI chromatin remodeling components ​Baz2a and ​Baz2b​, not previously implicated in regeneration. ​In vivo sgRNA, siRNA, and knockout strategies against either paralog confirmed increased regeneration. Distinct BAZ2-specific bromodomain inhibitors GSK2801 and BAZ2-ICR resulted in accelerated liver healing after diverse injuries. Inhibitor treated mice also exhibited improved regeneration in an inflammatory bowel disease model, suggesting multi-tissue applicability. Transcriptomics on regenerating livers showed increases in ribosomal and cell cycle mRNAs. Surprisingly, CRISPRa screening to define mechanisms showed that overproducing ribosomal proteins was sufficient to drive regeneration, while ​Rpl24 haploinsufficiency was rate limiting for BAZ2 inhibition mediated regeneration. The discovery of regenerative roles for imitation-SWI components provides immediate strategies to enhance tissue repair.
 
Overall design Examination of changes in chromatin accessbility after BAZ2 inhibition
 
Contributor(s) Jia Y, Zhu H
Citation(s)
  • Jia Y, Li L, Lin YH, Gopal P et al. In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration. Cell Stem Cell 2022 Mar 3;29(3):372-385.e8. PMID: 35090595
Submission date Sep 06, 2021
Last update date Apr 26, 2022
Contact name Hao Zhu
E-mail(s) yuemeng.jia@utsouthwestern.edu
Organization name UT Southwestern Medical Cetern
Street address 6000 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75202
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM5558371 H2.35 cells treated with GSK8573 - rep1
GSM5558372 H2.35 cells treated with GSK8573 - rep2
GSM5558373 H2.35 cells treated with GSK8573 - rep3
This SubSeries is part of SuperSeries:
GSE183502 In vivo CRISPR screening reveals druggable regulators of mammalian tissue regeneration
Relations
BioProject PRJNA761083
SRA SRP335827

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Supplementary file Size Download File type/resource
GSE183497_RAW.tar 1.9 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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