Activation of Hematopoietic Stem and Progenitor Cells in Cardiovascular and Metabolic Diseases

Splenic HSC exhibit a pre-activated phenotype | Unlike quiescent bone marrow hematopoietic stem cells, most of splenic HSC are in the G1 phase of the cell cycle, indicating their pre-activated phenotype. Congruently, in the acute phase of inflammatory conditions, splenic but not bone marrow HSC enter the S-G2-M phase of the cell cycle. The splenic microenvironment plays an important role in HSC pre-activation, and myeloid translocation gene 16 acts as a negative regulator of G1-S transition of splenic HSC.

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.

Selected Publications

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 ( and Matthias Nahrendorf (

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 ( and Matthias Nahrendorf (