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Publication
Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells.
Authors Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, Silberstein L,
Heidt T, Sebas M, Sun Y, Wojtkiewicz G, Feruglio PF, King K, Baker JN, van der
Laan AM, Borodovsky A, Fitzgerald K, Hulsmans M, Hoyer F, Iwamoto Y, Vinegoni C,
Brown D, Di Carli M, Libby P, Hiebert SW, Scadden DT, Swirski FK, Weissleder R,
Nahrendorf M
Submitted By Partha Dutta on 7/24/2015
Status Published
Journal Cell stem cell
Year 2015
Date Published 5/7/2015
Volume : Pages 16 : 477 - 487
PubMed Reference 25957903
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.




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