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

AUTHORS

Dutta PPartha , Sager HBHendrik B , Stengel KRKristy R , Naxerova KKamila , Courties GGabriel , Saez BBorja , Silberstein LLev , Heidt TTimo , Sebas MMatthew , Sun YYuan , Wojtkiewicz GGregory , Feruglio PFPaolo Fumene , King KKevin , Baker JNJoshua N , van der Laan AMAnja M , Borodovsky AAnna , Fitzgerald KKevin , Hulsmans MMaarten , Hoyer FFriedrich , Iwamoto YYoshiko , Vinegoni CClaudio , Brown DDennis , Di Carli MMarcelo , Libby PPeter , Hiebert SWScott W , Scadden DTDavid T , Swirski FKFilip K , Weissleder RRalph , Nahrendorf MMatthias . Cell stem cell. 2015 5 7; 16(5). 477-87

PMID: 25957903[PubMed].
PMCID: PMC4426344.

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.