Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells

Authors

Dutta P Partha , Sager HB Hendrik B , Stengel KR Kristy R , Naxerova K Kamila , Courties G Gabriel , Saez B Borja , Silberstein L Lev , Heidt T Timo , Sebas M Matthew , Sun Y Yuan , Wojtkiewicz G Gregory , Feruglio PF Paolo Fumene , King K Kevin , Baker JN Joshua N , van der Laan AM Anja M , Borodovsky A Anna , Fitzgerald K Kevin , Hulsmans M Maarten , Hoyer F Friedrich , Iwamoto Y Yoshiko , Vinegoni C Claudio , Brown D Dennis , Di Carli M Marcelo , Libby P Peter , Hiebert SW Scott W , Scadden DT David T , Swirski FK Filip K , Weissleder R Ralph , Nahrendorf M Matthias .
Cell stem cell. 2015 5 7; 16(5).
477-87

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.