Hagedorn EJ, Perlin JR, Freeman RJ, Wattrus SJ, Han T, Mao C, Kim JW, Fernández-Maestre I, Daily ML, D'Amato C, Fairchild MJ, Riquelme R, Li B, Ragoonanan DAVE, Enkhbayar K, Henault EL, Wang HG, Redfield SE, Collins SH, Lichtig A, Yang S, Zhou Y, Kunar B, Gomez-Salinero JM, Dinh TT, Pan J, Holler K, Feldman HA, Butcher EC, van Oudenaarden A, Rafii S, Junker JP, Zon LI. 2023. Transcription factor induction of vascular blood stem cell niches in vivo. Developmental cell. 58(12):1037-1051.e4. Pubmed: 37119815 DOI:S1534-5807(23)00160-0


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.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Related Faculty

Photo of Len Zon

The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.

Search Menu