Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.

Autor:	Binder V; Dr. von Hauner Childrens' Hospital, University Hospital Ludwig Maximillian's University, Department of Pediatric Hematology/Oncology, 80337 Munich, Germany., Li W; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Faisal M; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Oyman K; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Calkins DL; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Shaffer J; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Teets EM; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Sher S; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Magnotte A; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Belardo A; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Deruelle W; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Gregory TC; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; The Ohio State University College of Medicine, Department of Biomedical Informatics, Columbus, OH 43210, USA., Orwick S; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Hagedorn EJ; Boston University School of Medicine, Department of Medicine, Boston, MA 02118, USA., Perlin JR; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Avagyan S; Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA 02115, USA., Lichtig A; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Barrett F; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Ammerman M; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Yang S; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Zhou Y; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA., Carson WE; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Shive HR; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Blachly JS; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; The Ohio State University College of Medicine, Department of Biomedical Informatics, Columbus, OH 43210, USA., Lapalombella R; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA., Zon LI; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA; Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, MA 02138, USA., Blaser BW; The Ohio State University College of Medicine, Department of Internal Medicine, Division of Hematology, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA. Electronic address: bradley.blaser@osumc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 May 30; Vol. 42 (5), pp. 112528. Date of Electronic Publication: 2023 May 18.
DOI:	10.1016/j.celrep.2023.112528
Abstrakt:	Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-δ, encoded by prkcda) increases the number of HSC clones by up to 80% and expands polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augment HSC competition for residency within the niche and expand defined niche populations. CXCL8 induces association of PKC-δ with the focal adhesion complex, activating extracellular signal-regulated kinase (ERK) signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche that is controlled by CXCL8 and PKC and has significant impact on HSC phylogenetic and phenotypic fate. Competing Interests: Declaration of interests L.I.Z. is a founder and stockholder of Fate Therapeutics, CAMP4 Therapeutics, Amagma Therapeutics, Scholar Rock, and Branch Biosciences. He is a consultant for Celularity and Cellarity. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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