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

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
Cell Stem Cell. 2015 16 (5): 477-87

PMID: 25957903 · PMCID: PMC4426344 · DOI:10.1016/j.stem.2015.04.008

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (18)

Animals Cell Movement Cells, Cultured Hematopoietic Stem Cells Macrophages Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Models, Animal Monocytes Myeloid Cells Myelopoiesis Myocardial Infarction Nuclear Proteins Receptors, CCR2 RNA, Small Interfering Transcription Factors Wound Healing

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