[PDF][PDF] Pten cell autonomously modulates the hematopoietic stem cell response to inflammatory cytokines

SN Porter, AS Cluster, RAJ Signer, J Voigtmann… - Stem cell reports, 2016 - cell.com
SN Porter, AS Cluster, RAJ Signer, J Voigtmann, DA Monlish, LG Schuettpelz, JA Magee
Stem cell reports, 2016cell.com
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 …
Summary
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.
cell.com