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Cell Stem Cell. 2015 May 7;16(5):477-87. doi: 10.1016/j.stem.2015.04.008.

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

Author information

1
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA. Electronic address: dutta.partha@mgh.harvard.edu.
2
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
3
Department of Biochemistry, Vanderbilt School of Medicine, Nashville, TN 37235, USA.
4
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02144, USA.
5
Center for Regenerative Medicine, Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
6
Department of Cardiac Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02144, USA.
7
Department of Cardiology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, Amsterdam, the Netherlands.
8
Alnylam Pharmaceuticals, 300 Third Street, Cambridge, MA 02142, USA.
9
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
10
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
11
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
12
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA. Electronic address: mnahrendorf@mgh.harvard.edu.

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.

PMID:
25957903
PMCID:
PMC4426344
DOI:
10.1016/j.stem.2015.04.008
[Indexed for MEDLINE]
Free PMC Article

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