The STAT3 Signaling Pathway affects Sca1+ Bone-associated Progenitors in the Hematopoetic Stem Cell Niche
- Xingbin Hu, Postdoctoral Fellow, City of Hope
- Ching-Cheng Chen, Principal Investigator, City of Hope
The hematopoetic niche is the core regulation machinery for hematopoietic stem cell (HSC) differentiation and self-renewal in bone marrow. STAT3 is a highly conserved signaling pathway that is involved in cell proliferation and cell cycle, but it is not yet known whether the STAT3 signal is a definite player in niche constitution. We previously confirmed that Sca1+ bone associated progenitors can differentiate into stroma lineages to maintain HSCs. This study aims to functionally characterize the role of the STAT3 signal on Sca1+ cells and their function in the hematopoetic niche. A transgenic osteotrix:STAT3 knockout mouse model was used for analysis. By flow cytometry, Sca1+ populations were isolated and examined. It was observed that STAT3 knockout populations exhibited increased myeloid lineages in peripheral blood and spleen samples. The myeloid lineage changes are believed to be a result of the Sca1+ bone associated progenitors because, firstly, the osteotrix:STAT3 knockout mice exhibited significantly increased Sca1+ sub-populations, and secondly, the down-regulated STAT3 Sca1+ cells co-cultured long-term improved the HSCs' engraftment in bone marrow transplantation assays. It was also observed in vitro that down-regulated STAT3 Sca1+ cells’ proliferation also rose. This observation is consistent with the earlier findings that Sca1+ populations increase when STAT3 is down-regulated or knocked out. This study is significant in clarifying how the STAT3 pathway participates in the niche constitution, a key component in HSC maintenance.