Zhao, Jimmy L. and Ma, Chao and O'Connell, Ryan M. and Mehta, Arnav and DiLoreto, Race and Heath, James R. and Baltimore, David (2014) Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis. Cell Stem Cell, 14 (4). pp. 445-459. ISSN 1934-5909. http://resolver.caltech.edu/CaltechAUTHORS:20140227-222713478
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During an infection, the body increases the output of mature immune cells 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 amount of diverse cytokines through the 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 a novel property of HSPCs that enables them to convert danger signals into versatile cytokine signals for regulation of stress hematopoiesis.
|Additional Information:||© 2014 Elsevier Inc. Received: October 1, 2013. Revised: November 28, 2013. Accepted: January 14, 2014. Published: February 20, 2014. The authors wish to thank Caltech animal facility and flow cytometry core facility and Drs. Alejandro Balazs, Devdoot Majumdar, and Michael Bethune of the D.B. lab for their help. RELA-GFP knockin and NF-kB-eGFP reporter mice were obtained from Dr. Manolis Pasparakis of the University of Cologne and Dr. Christian Jobin of the University of North Carolina, respectively. The work was supported by research grants R01AI079243 (D.B.), R01CA170689 (J.R.H.), National Research Service Award F30HL110691 (J.L.Z.), UCLA/Caltech Medical Scientist Training Program (J.L.Z. and A.M.), Rosen Fellowship (C.M.), NIH New Innovator Award DP2GM111099 (R.M.O.), the Pathway to Independence Award R00HL102228 (R.M.O.), and an American Cancer Society Research grant (R.M.O.) with core facilities support from 5U54CA119347 (J.R.H.).|
|Official Citation:||Jimmy L. Zhao, Chao Ma, Ryan M. O’Connell, Arnav Mehta, Race DiLoreto, James R. Heath, David Baltimore, Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis, Cell Stem Cell, Volume 14, Issue 4, 3 April 2014, Pages 445-459, ISSN 1934-5909, http://dx.doi.org/10.1016/j.stem.2014.01.007. (http://www.sciencedirect.com/science/article/pii/S1934590914000083)|
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|Deposited On:||28 Feb 2014 06:47|
|Last Modified:||28 May 2014 21:57|
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