Transcription factor induction of vascular blood stem cell niches in vivo.

Autor:	Hagedorn EJ; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA; Section of Hematology and Medical Oncology and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Perlin JR; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Freeman RJ; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Wattrus SJ; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Han T; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Mao C; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Kim JW; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Fernández-Maestre I; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Daily ML; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., D'Amato C; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Fairchild MJ; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Riquelme R; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Li B; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Ragoonanan DAVE; Section of Hematology and Medical Oncology and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Enkhbayar K; Section of Hematology and Medical Oncology and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Henault EL; Section of Hematology and Medical Oncology and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Wang HG; Section of Hematology and Medical Oncology and Center for Regenerative Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA., Redfield SE; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Collins SH; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Lichtig A; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Yang S; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Zhou Y; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA., Kunar B; Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Gomez-Salinero JM; Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Dinh TT; Veterans Affairs Palo Alto Health Care System, The Palo Alto Veterans Institute for Research and the Department of Pathology, Stanford University, Stanford, CA, USA., Pan J; Veterans Affairs Palo Alto Health Care System, The Palo Alto Veterans Institute for Research and the Department of Pathology, Stanford University, Stanford, CA, USA., Holler K; Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, Germany., Feldman HA; Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA., Butcher EC; Veterans Affairs Palo Alto Health Care System, The Palo Alto Veterans Institute for Research and the Department of Pathology, Stanford University, Stanford, CA, USA., van Oudenaarden A; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, the Netherlands., Rafii S; Ansary Stem Cell Institute, Division of Regenerative Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Junker JP; Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, Germany., Zon LI; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA, USA. Electronic address: zon@enders.tch.harvard.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2023 Jun 19; Vol. 58 (12), pp. 1037-1051.e4. Date of Electronic Publication: 2023 Apr 28.
DOI:	10.1016/j.devcel.2023.04.007
Abstrakt:	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. Competing Interests: Declaration of interests L.I.Z. is a founder and stockholder of Fate Therapeutics, CAMP4 Therapeutics, and Scholar Rock. He is a consultant for Celularity. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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