In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
23 Jul 2024
23 Jul 2024
Historique:
received:
21
12
2023
accepted:
15
07
2024
revised:
10
07
2024
medline:
24
7
2024
pubmed:
24
7
2024
entrez:
23
7
2024
Statut:
aheadofprint
Résumé
Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen. Using this experimental system, we identified the TFDP1 transcription factor to be essential for HSPC proliferation and post-transplant hematopoiesis. We further discovered that E2F4, an E2F transcription factor, serves as a binding partner of TFDP1 and is required for HSPC proliferation. Deletion of TFDP1 caused downregulation of genes associated with the cell cycle, with around 50% of these genes being identified as direct targets of TFDP1 and E2F4. Thus, our study expands the transcriptional network governing hematopoietic development through an in vivo CRISPR/Cas9-based genetic screen and identifies TFDP1/E2F4 as positive regulators of cell cycle genes in HSPCs.
Identifiants
pubmed: 39043964
doi: 10.1038/s41375-024-02357-w
pii: 10.1038/s41375-024-02357-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CH 1968/1-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CH 1968/1-1
Organisme : Helmholtz Association
ID : ZT-0027
Informations de copyright
© 2024. The Author(s).
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