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| Status |
Public on Jul 09, 2024 |
| Title |
Baf155 establishes chromatin priming to promote hematopoietic regeneration and function [single cell multiome - ATAC + GEX] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromatin priming promotes cell type-specific gene expression, lineage differentiation, and development. The mechanism of chromatin priming has not been well understood. Mouse hematopoietic stem and progenitor cells (HSPCs) lacking the Baf155 subunit of the BAF (BRG1/BRM associated factor) chromatin-remodeler produced a significantly reduced number of mature blood cells, leading to a failure of hematopoietic regeneration upon transplantation and 5-FU injury. Baf155 deficient HSPCs, while showing impaired mature blood cell production, generated a higher frequency of myeloid cells with fewer B and CD8+ T cells at homeostasis, supporting a more immune-suppressive tumor microenvironment and enhanced tumor growth. Single-nuclei multi-omic analysis revealed that Baf155 deficient HSPCs failed to establish accessible chromatin and levels of lineage-specific transcripts were considerably lower. Regions that showed a substantial loss in chromatin accessibility were enriched for enhancers and binding motifs for hematopoietic lineage-specific transcription factors. Our study provides a fundamental mechanistic understanding of the role of Baf155 in establishing chromatin priming with functional consequences in regeneration or tumor immunity.
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| Overall design |
single cell multiome ATAC + GEX assays were performed on WT and Baf155 KO HSPCs, 9 or 11 days after 5FU injury.
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| Contributor(s) |
Wu J, Fan C, Xing X, Wang T, Choi K |
| Citation(s) |
39088321 |
| |
| Submission date |
Aug 10, 2023 |
| Last update date |
Oct 08, 2024 |
| Contact name |
Changxu Fan |
| E-mail(s) |
fanc@wustl.edu
|
| Organization name |
Washington University in St. Louis
|
| Department |
Genetics
|
| Lab |
Ting Wang Lab
|
| Street address |
4515 McKinley Avenue, Room 5213
|
| City |
Saint Louis |
| State/province |
Missouri |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE240585 |
Baf155 controls hematopoietic differentiation and regeneration through chromatin priming |
|
| Relations |
| BioProject |
PRJNA1004272 |
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