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

Partha Dutta; Hendrik B. Sager; Kristy R. Stengel; Kamila Naxerova; Gabriel Courties; Borja Saez; Lev Silberstein; Timo Heidt; Matthew Sebas; Yuan Sun; Gregory Wojtkiewicz; Paolo Fumene Feruglio; Kevin King; Joshua N. Baker; Anja M. van der Laan; Anna Borodovsky; Kevin Fitzgerald; Maarten Hulsmans; Friedrich Hoyer; Yoshiko Iwamoto; Claudio Vinegoni; Dennis Brown; Marcelo Di Carli; Peter Libby; Scott W. Hiebert; David T. Scadden; Filip K. Swirski; Ralph Weissleder; Matthias Nahrendorf

doi:https://doi.org/10.1016/j.stem.2015.04.008

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

Partha Dutta, Hendrik B. Sager, Kristy R. Stengel, Kamila Naxerova, Gabriel Courties, Borja Saez, Lev Silberstein, Timo Heidt, Matthew Sebas, Yuan Sun, Gregory Wojtkiewicz, Paolo Fumene Feruglio, Kevin King, Joshua N. Baker, Anja M. van der Laan, Anna Borodovsky, Kevin Fitzgerald, Maarten Hulsmans, Friedrich Hoyer, Yoshiko IwamotoClaudio Vinegoni, Dennis Brown, Marcelo Di Carli, Peter Libby, Scott W. Hiebert, David T. Scadden, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf

Cardiology (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

158 Citations (Scopus)

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

Original language	English
Pages (from-to)	477-487
Journal	Cell Stem Cell
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.stem.2015.04.008
Publication status	Published - 2015

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https://doi.org/10.1016/j.stem.2015.04.008

Cite this

Dutta, P., Sager, H. B., Stengel, K. R., Naxerova, K., Courties, G., Saez, B., Silberstein, L., Heidt, T., Sebas, M., Sun, Y., Wojtkiewicz, G., Feruglio, P. F., King, K., Baker, J. N., van der Laan, A. M., Borodovsky, A., Fitzgerald, K., Hulsmans, M., Hoyer, F., ... Nahrendorf, M. (2015). Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells. Cell Stem Cell, 16(5), 477-487. https://doi.org/10.1016/j.stem.2015.04.008

@article{5dac60f701074bce80fe4fe8a90c02c5,

title = "Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells",

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",

author = "Partha Dutta and Sager, {Hendrik B.} and Stengel, {Kristy R.} and Kamila Naxerova and Gabriel Courties and Borja Saez and Lev Silberstein and Timo Heidt and Matthew Sebas and Yuan Sun and Gregory Wojtkiewicz and Feruglio, {Paolo Fumene} and Kevin King and Baker, {Joshua N.} and {van der Laan}, {Anja M.} and Anna Borodovsky and Kevin Fitzgerald and Maarten Hulsmans and Friedrich Hoyer and Yoshiko Iwamoto and Claudio Vinegoni and Dennis Brown and {Di Carli}, Marcelo and Peter Libby and Hiebert, {Scott W.} and Scadden, {David T.} and Swirski, {Filip K.} and Ralph Weissleder and Matthias Nahrendorf",

year = "2015",

doi = "https://doi.org/10.1016/j.stem.2015.04.008",

language = "English",

volume = "16",

pages = "477--487",

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issn = "1934-5909",

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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 2015, 'Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells', Cell Stem Cell, vol. 16, no. 5, pp. 477-487. https://doi.org/10.1016/j.stem.2015.04.008

TY - JOUR

T1 - Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells

AU - Dutta, Partha

AU - Sager, Hendrik B.

AU - Stengel, Kristy R.

AU - Naxerova, Kamila

AU - Courties, Gabriel

AU - Saez, Borja

AU - Silberstein, Lev

AU - Heidt, Timo

AU - Sebas, Matthew

AU - Sun, Yuan

AU - Wojtkiewicz, Gregory

AU - Feruglio, Paolo Fumene

AU - King, Kevin

AU - Baker, Joshua N.

AU - van der Laan, Anja M.

AU - Borodovsky, Anna

AU - Fitzgerald, Kevin

AU - Hulsmans, Maarten

AU - Hoyer, Friedrich

AU - Iwamoto, Yoshiko

AU - Vinegoni, Claudio

AU - Brown, Dennis

AU - Di Carli, Marcelo

AU - Libby, Peter

AU - Hiebert, Scott W.

AU - Scadden, David T.

AU - Swirski, Filip K.

AU - Weissleder, Ralph

AU - Nahrendorf, Matthias

PY - 2015

Y1 - 2015

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.stem.2015.04.008

DO - https://doi.org/10.1016/j.stem.2015.04.008

M3 - Article

C2 - 25957903

SN - 1934-5909

VL - 16

SP - 477

EP - 487

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 5

ER -