Associate Professor Fujita Health University, Japan
Abstract: Hematopoietic stem/progenitor cells (HSPCs) maintain the homeostasis of the hematopoietic system in the bone marrow (BM). The ability of HSPCs to engraft and sustain long-term hematopoiesis is fundamental to the stem cell system in the bone marrow. BM transplantation therapy promotes platelet generation and early neutrophil differentiation, thereby reducing the risk of infection. Furthermore, the administration of stimulating factors during HSPC transplantation can induce the differentiation of myeloid cells. However, the factors that contribute to lineage determination in BM or transplanted cells remain unclear.
In this study, we aimed to elucidate the effects of Mesenchymal stem/stromal cells (MSCs) on HSPC differentiation. To achieve this, HSPCs and MSCs were purified using a flow cytometer, and in vitro co-culture experiments were performed. The results showed that activated MSCs secrete the chemokine CCL2, which regulates the differentiation ability of HSPCs and promotes the production of myeloid cells. When CCL2 was knocked out in MSCs, the ability of HSPCs to differentiate into myeloid cells was significantly reduced.
The main cell cluster secreting CCL2 upon lipopolysaccharide (LPS) stimulation was MSCs, which were found to regulate differentiation induction by targeting granulocyte/macrophage progenitors. Single-cell RNA sequencing analysis revealed that the stimulation of CCL2 significantly enhances the expression of RAS, highlighting its critical role. MSCs function as sensors for inflammation and infection and are thought to transmit inflammatory signals to hematopoietic cells in vivo. These findings support a model in which MSCs promote the recovery of essential immune cell compartments through CCL2 signaling.
Funding Source: This work was financially supported by the AMED (grant numbers 23bm1223011h0001); the JST, CREST Japan (grant number JPMJCR2124).
