Myocardial Infarction Activates CCR2+ Hematopoietic Stem and Progenitor Cells

被引：200

作者：

Dutta, Partha ^{[1
,2
]}

Sager, Hendrik B. ^{[1
,2
]}

Stengel, Kristy R. ^{[3
]}

Naxerova, Kamila ^{[4
]}

Courties, Gabriel ^{[1
,2
]}

Saez, Borja ^{[5
]}

Silberstein, Lev ^{[5
]}

Heidt, Timo ^{[1
,2
]}

Sebas, Matthew ^{[1
,2
]}

Sun, Yuan ^{[1
,2
]}

Wojtkiewicz, Gregory ^{[1
,2
]}

Fumene Feruglio, Paolo ^{[1
,2
]}

King, Kevin ^{[1
,2
]}

Baker, Joshua N. ^{[6
]}

van der Laan, Anja M. ^{[7
]}

Borodovsky, Anna ^{[8
]}

Fitzgerald, Kevin ^{[8
]}

Hulsmans, Maarten ^{[1
,2
]}

Hoyer, Friedrich ^{[1
,2
]}

Iwamoto, Yoshiko ^{[1
,2
]}

Vinegoni, Claudio ^{[1
,2
]}

Brown, Dennis ^{[1
,2
]}

Di Carli, Marcelo ^{[9
]}

Libby, Peter ^{[10
]}

Hiebert, Scott W. ^{[3
]}

Scadden, David T. ^{[5
]}

Swirski, Filip K. ^{[1
,2
]}

Weissleder, Ralph ^{[1
,2
,11
]}

Nahrendorf, Matthias ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN 37235 USA

[4] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02144 USA

[5] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[6] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02144 USA

[7] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands

[8] Alnylam Pharmaceut, Cambridge, MA 02142 USA

[9] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA

[10] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2015年 / 16卷 / 05期

关键词：

BONE-MARROW; MONOCYTE EMIGRATION; SELF-RENEWAL; IN-VIVO; ATHEROSCLEROSIS; IDENTIFICATION; PROLIFERATION; INFLAMMATION; MACROPHAGES; MECHANISMS;

D O I：

10.1016/j.stem.2015.04.008

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：477 / 487

页数：11

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