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Cited by 22Hematopoietic Stem Cell TransplantationBlood disorders and treatmentsMesenchymal stem cell research

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

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Porter, Shaina N., Cluster, Andrew S., Signer, Robert A.J., Voigtmann, Jenna, Monlish, Darlene A., Schuettpelz, Laura G., Magee, Jeffrey A.·2016·Stem Cell Reports
DOI 10.1016/j.stemcr.2016.04.008PMC PMC4911494
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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.

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  • Deletion of Pten leads to aberrant HSC activity and hypersensitivity to inflammatory factors such as G-CSF and IFN.

    “deletion of Pten, which dephosphorylates and inhibits the eIF activator mammalian target of rapamycin, leads to similar aberrant HSC activity and hypersensitivity to inflammatory factors, such as G-CSF and IFN (Porter et al., 2016; Signer et al., 2014)”

    From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Porter et al., 2016

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Authors
Porter, S. N., Cluster, A. S., Signer, R. A. J., Voigtmann, J., Monlish, D. A., Schuettpelz, L. G., & Magee, J. A.
Affiliations
  • Washington University in St. Louis (US)
  • University of California San Diego (US)
Corresponding author
Magee, Jeffrey A.
ORCID
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2016-06
Volume
6
Issue
6
Pages
806-814
ISSN
2213-6711 (ISSN-L)
DOI
10.1016/j.stemcr.2016.04.008
PMC
PMC4911494
OpenAlex
W2383089662
Cited by
22
References
1
Citations by year
2026: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • St. Baldrick's Foundation
  • Department of Pediatrics, University of Florida (5T32HD043010-12)
  • U.S. Department of Defense (CA130124)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
PTEN, hematopoietic stem cells, cell-autonomous regulation, non-cell-autonomous regulation, PI3K signaling, hematopoietic stem cell mobilization, granulocyte colony-stimulating factor, interferon-alpha, inflammatory cytokines, HSC quiescence, HSC proliferation, spleen
MeSH terms
Animals, Fetus, Gene Expression Regulation, Hematopoietic Stem Cells, Mice, Transgenic, Spleen, Signal Transduction, Granulocyte Colony-Stimulating Factor, Interferon-alpha, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cell Mobilization, Phosphatidylinositol 3-Kinases, Cell Proliferation, PTEN Phosphohydrolase, Mice

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