EBF1 primes B-lymphoid enhancers and limits the myeloid bias in murine multipotent progenitors
Abstract: Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) generate all cells of the blood system. Despite their multipotency, MPPs display poorly understood lineage bias. Here, we examine whether lineage-specifying transcription factors, such as the B-lineage determinant EBF1, regulate lineage preference in early progenitors. We detect low-level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, coinciding with expression of the myeloid determinant C/EBPα. Hematopoietic deletion of Ebf1 results in enhanced myelopoiesis and reduced HSC repopulation capacity. Ebf1-deficient MPP3 and MPP4 cells exhibit an augmented myeloid differentiation potential and a transcriptome with an enriched C/EBPα signature. Correspondingly, EBF1 binds the Cebpa enhancer, and the deficiency and overexpression of Ebf1 in MPP3 and MPP4 cells lead to an up- and downregulation of Cebpa expression, respectively. In addition, EBF1 primes the chromatin of B-lymphoid enhancers specifically in MPP3 cells. Thus, our study implicates EBF1 in regulating myeloid/lymphoid fate bias in MPPs by constraining C/EBPα-driven myelopoiesis and priming the B-lymphoid fate
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Journal of experimental medicine. - 219, 11 (2022) , e20212437, ISSN: 1540-9538
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2024
- Urheber
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Lenaerts, Aurelie
Kucinski, Iwo
Deboutte, Ward
Derecka, Marta
Cauchy, Pierre
Manke, Thomas
Göttgens, Berthold
Grosschedl, Rudolf
- DOI
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10.1084/jem.20212437
- URN
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urn:nbn:de:bsz:25-freidok-2451201
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:43 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Lenaerts, Aurelie
- Kucinski, Iwo
- Deboutte, Ward
- Derecka, Marta
- Cauchy, Pierre
- Manke, Thomas
- Göttgens, Berthold
- Grosschedl, Rudolf
- Universität
Entstanden
- 2024
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