The Sca1+ mesenchymal stromal subpopulation promotes dendritic cell commitment in the niche

Authors: NA LI, DANDAN YIN, HUIJIE ZHANG, JINMEI XU, FAN WEN, ZHENG LIU, YAOZHEN CHEN, NING AN, JIAJIA XIN, YAZHOU WANG, WEN YIN, XINGBIN HU

Abstract: The hematopoietic microenvironment regulates self-renewal and differentiation of hematopoietic stem cells. Mesenchymal stromal cells (MSCs) contribute to the niche and participate in supporting dendritic cell (DC) commitment in vitro and in vivo. However, due to MSCs being heterogenic, it is necessary to understand the function of the MSC subpopulation in modulating the DC commitment. The current study showed that one of the bone-related Sca1⁺ MSCs enhanced bone marrow cell differentiation into DCs by direct cell-to-cell contact. Furthermore, the expression of STAT3 and STAT5 genes decreased in supernatant cells after Sca1+ MSCs were cocultured with bone marrow cells. In contrast, the expression level of caspase-3 in cells increased. At the same time, the presentation of costimulatory molecules CD80/CD86 and the migration of activated DCs towards lymph nodes were augmented by Sca1⁺ MSCs. The results demonstrated that the Sca1⁺ MSC subpopulation promotes the differentiation of bone marrow cells into DCs by direct cell-to-cell contact via STAT3/STAT5 and caspase-3 signaling. Meanwhile, Sca1⁺ MSCs also mediate the activation and migration capabilities of DCs.

Keywords: Caspase-3, development, dendritic cells, migration capability, Sca1⁺ mesenchymal stromal cells

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