Affymetrix Gene Expression profiles of murine LAMTOR2-deficient hematopoietic progenitor cells

LAMTOR2, a member of the Ragulator complex, controls endosomal signaling. Here, we show that postnatal Mx1-Cre-driven deletion of LAMTOR2 in mice resulted in the development of a cell-intrinsic myeloproliferation characterized by splenomegaly, accumulation of myelomonocytoid cells, and depletion of long-term hematopoietic stem cells. LAMTOR2-deficient hematopoietic progenitors exhibited a myeloid-skewed gene expression signature as well as an enhanced GM-CSF-mediated colony formation and activation of ERK signaling. In contrast, disruption of LAMTOR2 resulted in decreased G CSF-mediated STAT3 signaling and impaired granulocytic differentiation. LAMTOR2-defective cells showed aberrant multivesicular body formation, consistent with delayed degradation of activated cytokine receptors. Our study reveals a critical role of LAMTOR2 in regulating cytokine signaling during hematopoietic differentiation. LAMTOR2-deficient and wild-type hematopoietic progenitor cells (LSK: Lin- Sca1+c kit+; Granulocyte-Macrophage-Progitors/GMP: Lin-Sca1-c-kit+CD34+FcγR+) were sorted from mouse bone marrow 14 days after administration of pIpC. Deletion of Lamtor2 was confirmed by PCR Analysis. Total RNA was extracted from sorted LSK and GMP of three C57BL/6J Mx-Cre Lamtorwt/wt and three C57BL/6J Mx-Cre Lamtor2f/f mice.