Activation of Hematopoietic Stem and Progenitor Cells in Cardiovascular and Metabolic Diseases
Since inflammatory myeloid cells can determine disease pathogenesis, one of the major research interests in our lab is to understand the mechanisms of inflammatory myeloid cell production from hematopoietic stem and progenitor cells in cardiovascular disease. We found that myocardial infarction activates CCR2+ hematopoietic stem cells (HSC) and drive them into the cell cycle. As a result, HSC differentiate into inflammatory myeloid cells. Generation of CCR2+ HSC from CCR2– HSC in the bone marrow depends on the myeloid translocation gene 16. Because splenic myeloipoiesis is insidious to the progression of atherosclerosis, we investigated splenic HSC maintenance. We found that VCAM-1+ macrophages play a crucial role in splenic HSC maintenance and myelopoiesis. Recently, we have shown that, in contrast to bone marrow HSC, splenic HSC exhibit a preactivated phenotype and can readily differentiate into inflammatory myeloid cells after an acute injury.
Coppin E, Florentin J, Vasamsetti SB, Arunkumar A, Sembrat J, Rojas M, Dutta P. Splenic hematopoietic stem cells display a pre-activated phenotype. Immunol Cell Biol. (Epub ahead of print). PMID: 29526053
Dutta P*, Sager H, Stengel K, Naxerova K,……Libby P, Hiebert S, Scadden D, Swirski FK, Weissleder R, Nahrendorf M. 2015. Myocardial infarction activates CCR2+ hematopoietic stem cells. Cell Stem Cell 16: 477-87. PMCID: PMC4426344. *Correspondence: Partha Dutta (firstname.lastname@example.org) and Matthias Nahrendorf (email@example.com)
Dutta, P*., F. F. Hoyer, L. S. Grigoryeva, H. B. Sager, F. Leuschner, G. Courties, A. Borodovsky, T. Novobrantseva, V. M. Ruda, K. Fitzgerald, Y. Iwamoto, G. Wojtkiewicz, Y. Sun, N. Da Silva, P. Libby, D. G. Anderson, F. K. Swirski, R. Weissleder, and M. Nahrendorf. 2015. Macrophages retain hematopoietic stem cells in the spleen via VCAM-1 in atherosclerosis. Journal of Experimental Medicine 212: 497-512. PMCID: PMC4387283. *Correspondence: Partha Dutta (firstname.lastname@example.org) and Matthias Nahrendorf (email@example.com)