HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition
| Autor: | Thambyrajah, Roshana, Fadlullah Wilmot, Muhammad Zaki Hidaya, Proffitt, Martin, Patel, Rahima, Cowley, M., Kouskoff, Valerie, Lacaud, Georges |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Hemangioblasts
Histone Deacetylase 2 Histone Deacetylase 1 Dioxoles TGF-β signaling Biochemistry Article endothelial-to-hematopoietic transition Mice in vitro differentiation Transforming Growth Factor beta Genetics Animals AGM hemogenic endothelium lcsh:QH301-705.5 lcsh:R5-920 Manchester Cancer Research Centre ResearchInstitutes_Networks_Beacons/mcrc Endothelial Cells Cell Differentiation Cell Biology embryonic stem cells HDAC1 Hematopoiesis HDAC2 hematopoietic stem cells Histone Deacetylase Inhibitors lcsh:Biology (General) Benzamides lcsh:Medicine (General) Tgfβ signalling Endothelial to Hematopoietic Transition Gene Deletion epigenetic Signal Transduction Developmental Biology |
| Zdroj: | Thambyrajah, R, Fadlullah, M Z H, Proffitt, M, Patel, R, Cowley, S M, Kouskoff, V & Lacaud, G 2018, ' HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition ' Stem Cell Reports, vol 10, no. 4, pp. 1369-1383 . DOI: 10.1016/j.stemcr.2018.03.011 Stem Cell Reports Stem Cell Reports, Vol 10, Iss 4, Pp 1369-1383 (2018) Thambyrajah, R, Fadlullah Wilmot, M Z H, Proffitt, M, Patel, R, Cowley, M, Kouskoff, V & Lacaud, G 2018, ' HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition ', Stem Cell Reports, vol. 10, no. 4, pp. 1369-1383 . https://doi.org/10.1016/j.stemcr.2018.03.011 |
| DOI: | 10.1016/j.stemcr.2018.03.011 |
| Popis: | Summary The first hematopoietic stem and progenitor cells are generated during development from hemogenic endothelium (HE) through trans-differentiation. The molecular mechanisms underlying this endothelial-to-hematopoietic transition (EHT) remain poorly understood. Here, we explored the role of the epigenetic regulators HDAC1 and HDAC2 in the emergence of these first blood cells in vitro and in vivo. Loss of either of these epigenetic silencers through conditional genetic deletion reduced hematopoietic transition from HE, while combined deletion was incompatible with blood generation. We investigated the molecular basis of HDAC1 and HDAC2 requirement and identified TGF-β signaling as one of the pathways controlled by HDAC1 and HDAC2. Accordingly, we experimentally demonstrated that activation of this pathway in HE cells reinforces hematopoietic development. Altogether, our results establish that HDAC1 and HDAC2 modulate TGF-β signaling and suggest that stimulation of this pathway in HE cells would be beneficial for production of hematopoietic cells for regenerative therapies. Graphical Abstract Highlights • Deletion of Hdac1 or Hdac2 in hemogenic endothelium (HE) reduces hematopoiesis • Double KO of Hdac1 and Hdac2 abolishes hematopoiesis • TGF-β signaling is deregulated in Hdac1 or Hdac2 deleted HE • TGF-β signaling improves hematopoietic output from HE Thambyrajah et al. established a critical role for HDAC1 and HDAC2 in EHT and identified TGF-β signaling as one of the main pathways modulated by HDAC1 and HDAC2. Activation of TGF-β signaling improves hematopoietic development and would therefore be beneficial for production of hematopoietic cells for regenerative therapies. |
| Databáze: | OpenAIRE |
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