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|Title:||HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition|
Fadlullah, Muhammad Z. H.
Cowley, Shaun M.
|Publisher:||Elsevier (Cell Press)|
|Citation:||Stem Cell Reports, 2018, 10 (4), pp. 1369-1383|
|Abstract:||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.|
|Rights:||Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Description:||The sequencing read files from the RNA and ChIP sequencing are available through GEO: GSE101683. Supplemental Information includes Supplemental Experimental Procedures, seven figures, two tables, and five videos and can be found with this article online at https://doi.org/10.1016/j.stemcr.2018.03.011.|
|Appears in Collections:||Published Articles, Dept. of Molecular and Cell Biology|
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