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| Status |
Public on Jun 30, 2022 |
| Title |
EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Haematopoietic stem cells (HSC) and multipotent progenitor cells (MPP) generate all cells of the blood system, although cellular heterogeneity and bias in lineage potential have been observed. Here, we examined whether lineage-specific transcription factors, such as the B-lineage determinant EBF1, establish lineage bias in early progenitors. We detect low level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, and show that Ebf1-deficient animals display reduced HSC quiescence and repopulation capacity, enhanced myelopoiesis and enhanced myeloid differentiation potential of MPP3 and MPP4 cells. Bulk and single-cell RNA-seq analysis revealed a CEBPa-driven myeloid transcriptome in Ebf1-deficient progenitors, and we find that EBF1 binds and potentially antagonizes the haematopoietic Cebpa enhancer. In MPP3 cells, EBF1 additionally primes enhancers associated with B-lymphoid genes that gain expression in common lymphoid progenitors. Thus, our study identifies EBF1 as an important determinant in regulating the balance of myeloid versus lymphoid potential in the earliest hematopoietic progenitors.
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| Overall design |
Bulk ATAC seq from 5000 MPP3 and MPP4 cells, from Ebf1-wt Tie2Cre and Ebf1-flox Tie2Cre mice. 2 biological repliccates per genotype, per cell type.
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| Contributor(s) |
Lenaerts A, Deboutte W, Grosschedl R |
| Citation(s) |
36048017 |
| |
| Submission date |
Nov 17, 2021 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Aurelie Lenaerts |
| E-mail(s) |
lenaerts@ie-freiburg.mpg.de
|
| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Cellular and Molecular Immunology
|
| Lab |
Laboratory Rudolf Grosschedl
|
| Street address |
Stübeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE189078 |
EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism |
|
| Relations |
| BioProject |
PRJNA781258 |
| SRA |
SRP346605 |
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