title: Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis.
abstract: During an infection, the body increases the output of mature immune cells in order to fight off the pathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) can sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. Here, we have combined mouse models with a single-cell proteomics platform to show that, in response to Toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amounts of diverse cytokines through nuclear factor κB (NF-κB) signaling. Interestingly, the cytokine production ability of HSPCs trumps mature immune cells in both magnitude and breadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid myeloid cell recovery during neutropenia. This study has uncovered an important property of HSPCs that enables them to convert danger signals into versatile cytokine signals for the regulation of stress hematopoiesis.
authors.affiliation: Division of Biology, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: NanoSystems Biology Cancer Center, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Pathology, University of Utah, 15 North Medical Drive East, Salt Lake City, UT 84112, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.affiliation: Division of Biology, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: Arnav
authors.initials: A
authors.lastname: Mehta
authors.affiliation: NanoSystems Biology Cancer Center, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: Race
authors.initials: R
authors.lastname: DiLoreto
authors.affiliation: NanoSystems Biology Cancer Center, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.|Kavli Nanoscience Institute, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
authors.affiliation: Division of Biology, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051193:Toll-Like Receptors