Myocardial infarction activates CCR2+ hematopoietic stem and progenitor cells

Partha Dutta, Hendrik B. Sager, Kristy R. Stengel, Kamila Naxerova, Gabriel Courties, Borja Saez, Lev Silberstein, Timo Heidt, Matthew Sebas, Yuan Sun, Gregory Wojtkiewicz, Paolo Fumene Feruglio, Kevin King, Joshua N. Baker, Anja M. Van Der Laan, Anna Borodovsky, Kevin Fitzgerald, Maarten Hulsmans, Friedrich Hoyer, Yoshiko IwamotoClaudio Vinegoni, Dennis Brown, Marcelo Di Carli, Peter Libby, Scott W. Hiebert, David T. Scadden, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these myeloid cells, and the response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is unclear. Here, we identify a CCR2+CD150+CD48- LSK hematopoietic subset as the most upstream contributor to emergency myelopoiesis after ischemic organ injury. This subset has 4-fold higher proliferation rates than CCR2-CD150+CD48- LSK cells, displays a myeloid differentiation bias, and dominates the migratory HSPC population. We further demonstrate that the myeloid translocation gene 16 (Mtg16) regulates CCR2+ HSPC emergence. Mtg16-/- mice have decreased levels of systemic monocytes and infarct-associated macrophages and display compromised tissue healing and post-MI heart failure. Together, these data provide insights into regulation of emergency hematopoiesis after ischemic injury and identify potential therapeutic targets to modulate leukocyte output after MI.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalCell Stem Cell
Volume16
Issue number5
DOIs
StatePublished - May 7 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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