biostudies-literatureYamazaki SCore Research for Evolutional Science and TechnologyTakeda Science FoundationJapan Agency for Medical Research and DevelopmentUehara Memorial FoundationJapan Science and Technology Agency414-425https://www.ebi.ac.uk/biostudies/studies/S-EPMC10937152biostudies-literatureUnknown19(3)Myeloid cells, which originate from hematopoietic stem/progenitor cells (HSPCs), play a crucial role in mitigating infections. This study aimed to explore the impact of mesenchymal stem/stromal cells (MSCs) on the differentiation of HSPCs and progenitors through the C-C motif chemokine CCL2/CCR2 signaling pathway. Murine MSCs, identified as PDGFRα⁺Sca-1⁺ cells (PαS cells), were found to secrete CCL2, particularly in response to lipopolysaccharide stimulation. MSC-secreted CCL2 promoted the differentiation of granulocyte/macrophage progenitors into the myeloid lineage. MSC-derived CCL2 plays an important role in the early phase of myeloid cell differentiation in vivo. Single-cell RNA sequencing analysis confirmed that CCL2-mediated cell fate determination was also observed in human bone marrow cells. These findings provide valuable insights for investigating the in vivo effects of MSC transplantation.Stem cell reportsActivated mesenchymal stem/stromal cells promote myeloid cell differentiation via CCL2/CCR2 signaling.PMC10937152JP20bm0404031h0103JP18KK0449JP21H03328JP18bm0404022h000123bm1223011h0001JPMJCR2124JP19KK0216JP19K10024Azuma YMabuchi YMorishita SKikuchi RSuto EGKimura TKondo AHisamatsu DAkazawa CKomatsu NNishikii HNaraoka YAraki MYamazaki SfalseActivated mesenchymal stem/stromal cells promote myeloid cell differentiation via CCL2/CCR2 signaling.Myeloid cells, which originate from hematopoietic stem/progenitor cells (HSPCs), play a crucial role in mitigating infections. This study aimed to explore the impact of mesenchymal stem/stromal cells (MSCs) on the differentiation of HSPCs and progenitors through the C-C motif chemokine CCL2/CCR2 signaling pathway. Murine MSCs, identified as PDGFRα⁺Sca-1⁺ cells (PαS cells), were found to secrete CCL2, particularly in response to lipopolysaccharide stimulation. MSC-secreted CCL2 promoted the differentiation of granulocyte/macrophage progenitors into the myeloid lineage. MSC-derived CCL2 plays an important role in the early phase of myeloid cell differentiation in vivo. Single-cell RNA sequencing analysis confirmed that CCL2-mediated cell fate determination was also observed in human bone marrow cells. These findings provide valuable insights for investigating the in vivo effects of MSC transplantation.2024-01-01T00:00:00Z2024 Mar2026-06-24T03:08:30.56Z2026-06-24T03:06:11.122ZS-EPMC109371523842841310.1016/j.stemcr.2024.02.002