| First Author | Qin Y | Year | 2019 |
| Journal | Stem Cell Res Ther | Volume | 10 |
| Issue | 1 | Pages | 210 |
| PubMed ID | 31311586 | Mgi Jnum | J:295550 |
| Mgi Id | MGI:6453953 | Doi | 10.1186/s13287-019-1311-0 |
| Citation | Qin Y, et al. (2019) Interferon gamma inhibits the differentiation of mouse adult liver and bone marrow hematopoietic stem cells by inhibiting the activation of notch signaling. Stem Cell Res Ther 10(1):210 |
| abstractText | BACKGROUND: The paradigm of hematopoietic stem and progenitor cells (HSPCs) has become accepted ever since the discovery of adult mouse liver hematopoietic stem cells and their multipotent characteristics that give rise to all blood cells. However, differences between bone marrow (BM) and liver hematopoietic stem cells and the hematopoietic microenvironment remain poorly understood. In addition, the regulation of the liver hematopoietic system remains unknown. METHODS: Clone formation assays were used to confirm that the proliferation of adult mouse liver and bone marrow HSPCs. Model mice with different interferon gamma (IFN-gamma) levels and a co-culture system were used to detect the differentiation of liver HSPCs. The gamma-secretase inhibitor (GSI) and the JAK/STAT inhibitor ruxolitinib and cell culture assays were used to explore the molecular mechanism by which IFN-gamma impairs HSPC proliferation and differentiation. RESULTS: The colony-forming activity of liver and bone marrow HSPCs was inhibited by IFN-gamma. Model mice with different IFN-gamma levels showed that the differentiation of liver HSPCs was impaired by IFN-gamma. Using a co-culture system comprising liver HSPCs, we found that IFN-gamma inhibited the development of liver hematopoietic stem cells into gammadeltaT cells. We then demonstrated that IFN-gamma might impair liver HSPC differentiation by inhibiting the activation of the notch signaling via the JAK/STAT signaling pathway. CONCLUSIONS: IFN-gamma inhibited the proliferation of liver-derived HSPCs. IFN-gamma also impaired the differentiation of long-term hematopoietic stem cells (LT-HSCs) into short-term hematopoietic stem cells (ST-HSCs) and multipotent progenitors (MPPs) and the process from LSK (Lineage(-)Sca-1(+)c-Kit(+)) cells to gammadeltaT cells. Importantly, we proposed that IFN-gamma might inhibit the activation of notch signaling through the JAK/STAT signaling pathway and thus impair the differentiation process of mouse adult liver and BM hematopoietic stem cells. |
