Claudio Vinegoni, Ph.D. | Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells

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

Dutta, P., Sager, H. B., Stengel, K. R., Naxerova, K., Courties, G., Saez, B., Silberstein, L., Heidt, T., Sebas, M., Sun, Y., Wojtkiewicz, G., Fumene Feruglio, P., King, K., Baker, J. N., Laan, A. M., Borodovsky, A., Fitzgerald, K., Hulsmans, M., Hoyer, F., Iwamoto, Y., Vinegoni, C., Brown, D., Di Carli, M., Libby, P., Hiebert, S. W., Scadden, D. T., Swirski, F. K., Weissleder, R., and Nahrendorf^#, M.

Cell Stem Cell 2015

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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.
@article{2015-CSC, author= {Dutta, P. and Sager, H. B. and Stengel, K. R. and Naxerova, K. and Courties, G. and Saez, B. and Silberstein, L. and Heidt, T. and Sebas, M. and Sun, Y. and Wojtkiewicz, G. and Fumene Feruglio, P. and King, K. and Baker, J. N. and van der Laan, A. M. and Borodovsky, A. and Fitzgerald, K. and Hulsmans, M. and Hoyer, F. and Iwamoto, Y. and Vinegoni, C. and Brown, D. and Di Carli, M. and Libby, P. and Hiebert, S. W. and Scadden, D. T. and Swirski, F. K. and Weissleder, R. and Nahrendorf<sup>#</sup>, M.}, title= {Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells}, journal= {Cell Stem Cell}, alternatejournal = {Cell Stem Cell}, year = {2015}, volume = {16}, number = {5}, pages = {477-487}, issn = {1934-5909}, doi = {10.1016/j.stem.2015.04.008}, pmcid = {PMC4426344}, pmid= {25957903} }
25957903

PMC4426344

10.1016/j.stem.2015.04.008

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."

Full citation

For attribution in academic contexts, please cite this work as:

Dutta, P., Sager, H. B., Stengel, K. R., Naxerova, K., Courties, G., Saez, B., Silberstein, L., Heidt, T., Sebas, M., Sun, Y., Wojtkiewicz, G., Fumene Feruglio, P., 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