Abstract
BackgroundThe 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.MethodsClone formation assays were used to confirm that the proliferation of adult mouse liver and bone marrow HSPCs. Model mice with different interferon gamma (IFN-γ) levels and a co-culture system were used to detect the differentiation of liver HSPCs. The γ-secretase inhibitor (GSI) and the JAK/STAT inhibitor ruxolitinib and cell culture assays were used to explore the molecular mechanism by which IFN-γ impairs HSPC proliferation and differentiation.ResultsThe colony-forming activity of liver and bone marrow HSPCs was inhibited by IFN-γ. Model mice with different IFN-γ levels showed that the differentiation of liver HSPCs was impaired by IFN-γ. Using a co-culture system comprising liver HSPCs, we found that IFN-γ inhibited the development of liver hematopoietic stem cells into γδT cells. We then demonstrated that IFN-γ might impair liver HSPC differentiation by inhibiting the activation of the notch signaling via the JAK/STAT signaling pathway.ConclusionsIFN-γ inhibited the proliferation of liver-derived HSPCs. IFN-γ 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 γδT cells. Importantly, we proposed that IFN-γ 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.
Highlights
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
The results showed that BrdU could be incorporated into liver and bone marrow (BM) LTHSCs, with more BrdU being incorporated into liver and BM Long-term hematopoietic stem cells (LT-Hematopoietic stem cells (HSCs)) from both IFN-γ-deficient mice (GKO) mice than into those of WT mice (Fig. 2e–g)
We found that the proportion of LSK cells in γ-Secretase inhibitor (GSI)-treated mice was reduced, and the proportion of LT-HSCs was significantly increased, while the proportion of Short-term hematopoietic stem cells (ST-HSC) and Multipotent progenitor (MPP) cells was decreased, which demonstrated that the development of HSPCs from LT-HSCs to ST-HSCs and MPPs was inhibited by blocking the notch signaling pathway (Fig. 7b)
Summary
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. Differences between bone marrow (BM) and liver hematopoietic stem cells and the hematopoietic microenvironment remain poorly understood. Bone marrow is the most important hematopoietic organ, which can replenish all blood cell types throughout life [4,5,6,7]. Transplantation experiments have shown that the HSCs in the liver retain their hematopoietic capacity and can differentiate into various mature immune cells [10, 13,14,15]. To some extent, these liver HSCs can provide compensatory hematopoiesis when bone marrow (BM) function is restrained [10]. The differences between BM and liver HSCs and the hematopoietic microenvironment are worthy of research attention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
