@article {Hagedorn2021.11.03.467105, author = {Elliott J. Hagedorn and Julie R. Perlin and Rebecca J. Freeman and Samuel J. Wattrus and Tianxiao Han and Clara Mao and Ji Wook Kim and In{\'e}s Fern{\'a}ndez-Maestre and Madeleine L. Daily and Christopher D{\textquoteright}Amato and Michael J. Fairchild and Raquel Riquelme and Brian Li and Dana A.V.E. Ragoonanan and Khaliun Enkhbayar and Emily L. Henault and Helen G. Wang and Shelby E. Redfield and Samantha H. Collins and Asher Lichtig and Song Yang and Yi Zhou and Balvir Kunar and Jesus Maria Gomez-Salinero and Thanh T. Dinh and Junliang Pan and Karoline Holler and Henry A. Feldman and Eugene C. Butcher and Alexander van Oudenaarden and Shahin Rafii and J. Philipp Junker and Leonard I. Zon}, title = {Transcription factor induction of vascular blood stem cell niches in vivo}, elocation-id = {2021.11.03.467105}, year = {2021}, doi = {10.1101/2021.11.03.467105}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The hematopoietic niche is a supportive microenvironment comprised 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, we define a conserved gene expression signature and cis-regulatory landscape unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code involving members of the Ets, Sox and Nuclear Hormone Receptor families that 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.Competing Interest StatementL.I.Z is a found and stockholder of Fate Therapeutics, CAMP4 Therapeutics and Scholar Rock. He is a consultant for Celularity. The authors declare no competing financial interests.}, URL = {https://www.biorxiv.org/content/early/2021/11/04/2021.11.03.467105}, eprint = {https://www.biorxiv.org/content/early/2021/11/04/2021.11.03.467105.full.pdf}, journal = {bioRxiv} }