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Stem Cell Reports. 2016 Jun 14;6(6):806-814. doi: 10.1016/j.stemcr.2016.04.008. Epub 2016 May 12.

Pten Cell Autonomously Modulates the Hematopoietic Stem Cell Response to Inflammatory Cytokines.

Author information

1
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8220, St. Louis, MO 63110, USA.
2
Division of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
3
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8220, St. Louis, MO 63110, USA. Electronic address: magee_j@kids.wustl.edu.

Abstract

Pten negatively regulates the phosphatidylinositol 3-kinase (PI3K) pathway and is required to maintain quiescent adult hematopoietic stem cells (HSCs). Pten has been proposed to regulate HSCs cell autonomously and non-cell autonomously, but the relative importance of each mechanism has not been directly tested. Furthermore, the cytokines that activate the PI3K pathway upstream of Pten are not well defined. We sought to clarify whether Pten cell autonomously or non-cell autonomously regulates HSC mobilization. We also tested whether Pten deficiency affects the HSC response to granulocyte colony-stimulating factor (G-CSF) and interferon-α (IFNα) since these cytokines induce HSC mobilization or proliferation, respectively. We show that Pten regulates HSC mobilization and expansion in the spleen primarily via cell-autonomous mechanisms. Pten-deficient HSCs do not require G-CSF to mobilize, although they are hyper-sensitized to even low doses of exogenous G-CSF. Pten-deficient HSCs are similarly sensitized to IFNα. Pten therefore modulates the HSC response to inflammatory cytokines.

PMID:
27185281
PMCID:
PMC4911494
DOI:
10.1016/j.stemcr.2016.04.008
[Indexed for MEDLINE]
Free PMC Article

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