STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice

Zan Huang, Terri D. Richmond, Andrew G. Muntean, Dwayne L. Barber, Mitchell J. Weiss, John D. Crispino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Thrombocytosis is associated with inflammation, and certain inflammatory cytokines, including IFN-γ, stimulate megakaryocyte and platelet production. However, the roles of IFN-γ and its downstream effector STAT1 in megakaryocyte development are poorly understood. We previously reported that STAT1 expression was significantly downregulated in Gata1-knockdown murine megakaryocytes, which also have impaired terminal maturation. Here, we show that ectopic expression of STAT1, or its target effector IRF-1, rescued multiple defects in Gata1-deficient megakaryopoiesis in mice, inducing polyploidization and expression of a subset of platelet-expressing genes. Enforced expression of STAT1, IRF-1, or GATA-1 enhanced phosphorylation of STAT1, STAT3, and STAT5 in cultured Gata1-deficient murine megakaryocytes, with concomitant megakaryocyte maturation. In contrast, enhanced thrombopoietin signaling, conferred by enforced expression of constitutively active JAK2 or c-MPL, induced phosphorylation of STAT3 and STAT5, but not STAT1, and failed to rescue megakaryocyte maturation. Finally, megakaryocytes from Stat1-/- mice were defective in polyploidization. Together, these findings reveal a unique role for STAT1 in megakaryopoiesis and provide new insights into how GATA-1 regulates this process. Our studies elucidate potential mechanisms by which various inflammatory disorders can cause elevated platelet counts.

Original languageEnglish (US)
Pages (from-to)3890-3899
Number of pages10
JournalJournal of Clinical Investigation
Issue number12
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Medicine(all)


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