In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis
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| Názov: | In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis |
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| Autori: | Ngoc Tung Tran, Robin Graf, Ernesto Acevedo-Ochoa, Janine Trombke, Timm Weber, Thomas Sommermann, Claudia Salomon, Ralf Kühn, Klaus Rajewsky, Van Trung Chu |
| Prispievatelia: | Pediatrics, School of Medicine |
| Zdroj: | Leukemia |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2024. |
| Rok vydania: | 2024 |
| Predmety: | 0301 basic medicine, Cancer Research, E2F4 Transcription Factor, Article, Transcription factor DP1, Mice, 03 medical and health sciences, Cell differentiation, Animals, Humans, Cell proliferation, Cell Proliferation, 0303 health sciences, Cell Cycle, 631/532/1542, 631/136/232, Hematopoietic Stem Cells/metabolism [MeSH], Mice, Inbred C57BL [MeSH], 42/41, 42, 38/91, Cell Cycle/genetics [MeSH], 38/39, 13/100, CRISPR-Cas Systems [MeSH], 13/31, 38/1, Hematopoietic Stem Cells/cytology [MeSH], E2F4 Transcription Factor/genetics [MeSH], Transcription Factor DP1/metabolism [MeSH], 13/2, Cell Proliferation [MeSH], Humans [MeSH], Transcription Factor DP1/genetics [MeSH], Cell Differentiation/genetics [MeSH], 13/106, Animals [MeSH], 64/60, 38/70, 13/44, Hematopoiesis/genetics [MeSH], Mice [MeSH], E2F4 Transcription Factor/metabolism [MeSH], 38, article, Cell Differentiation, Hematopoietic Stem Cells, Hematopoiesis, Mice, Inbred C57BL, Integrative Biomedicine [Topic 3], Technology Platforms, CRISPR-Cas Systems, Transcription Factor DP1, Hematopoietic stem cells |
| Popis: | 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. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/s41375-024-02357-w |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39043964 https://edoc.mdc-berlin.de/id/eprint/24553/2/24553suppl.zip https://repository.publisso.de/resource/frl:6491352 |
| Rights: | CC BY "In Copyright" Rights Statement |
| Prístupové číslo: | edsair.doi.dedup.....03508ccbebc32601b7433a135d785bf3 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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. |
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| ISSN: | 14765551 08876924 |
| DOI: | 10.1038/s41375-024-02357-w |