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Transcription factor induction of vascular blood stem cell niches in vivo

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Item Type:Article
Title:Transcription factor induction of vascular blood stem cell niches in vivo
Creators Name:Hagedorn, E.J. and Perlin, J.R. and Freeman, R.J. and Wattrus, S.J. and Han, T. and Mao, C. and Kim, J.W. and Fernández-Maestre, I. and Daily, M.L. and D'Amato, C. and Fairchild, M.J. and Riquelme, R. and Li, B. and Ragoonanan, D.A.V.E. and Enkhbayar, K. and Henault, E.L. and Wang, H.G. and Redfield, S.E. and Collins, S.H. and Lichtig, A. and Yang, S. and Zhou, Y. and Kunar, B. and Gomez-Salinero, J.M. and Dinh, T.T. and Pan, J. and Holler, K. and Feldman, H.A. and Butcher, E.C. and van Oudenaarden, A. and Rafii, S. and Junker, J.P. and Zon, L.I.
Abstract:The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.
Keywords:Hematopoietic Development, Blood Stem Cell Niche, Reprogramming, Vascular Endothelium, Niche Endothelial Cells, Animals, Zebrafish
Source:Developmental Cell
Publisher:Cell Press
Page Range:1037-1051
Date:19 June 2023
Official Publication:https://doi.org/10.1016/j.devcel.2023.04.007
PubMed:View item in PubMed

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