Abstract
It has been reported that the adult liver contains hematopoietic stem and progenitor cells (HSPCs), which are associated with long-term hematopoietic reconstitution activity. Hepatic hematopoiesis plays an important role in the generation of cells involved in liver diseases. However, how the progenitors differentiate into functional myeloid cells and lymphocytes in the liver microenvironment remains unknown. In the present study, HSPC transplantation experiments were used to confirm that adult murine liver HSPCs differentiate into both myeloid cells and lymphocytes (preferentially T cells) compared with bone marrow HSPCs. Using a coculture system comprised of kupffer cells and HSPCs, we found that kupffer cells promote adult liver HSPCs to primarily generate T cells and B cells. We then demonstrated that kupffer cells can also promote HSPC expansion. A blockade of intercellular cell adhesion molecule-1 (ICAM-1) in a liver HSPC and kupffer cell coculture system impaired the adhesion, expansion, and differentiation of HSPCs. These results suggest a critical role of kupffer cells in the maintenance and promotion of adult mouse liver hematopoiesis. These findings provide important insight into understanding liver extramedullary hematopoiesis and its significance, particularly under the state of some liver diseases, such as hepatitis, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC).
Highlights
It has been established that the liver is the major hematopoietic organ during fetal period
Hepatic hematopoiesis plays an important role in the generation of cells involved in tumor surveillance and rejection [8], there is a lack of systemic research comparing the differences between hematopoiesis and lymphogenesis between the adult liver and bone marrow and how the liver microenvironment contributes to these events
We found that kupffer cells could induce liver hematopoietic stem and progenitor cells (HSPCs) to differentiate into a relatively high proportion of T and B lymphocytes in an intercellular cell adhesion molecule-1 (ICAM-1)/LFA-1 interaction-dependent manner
Summary
It has been established that the liver is the major hematopoietic organ during fetal period. It has been reported that the adult liver contains Linlo/-sca-1+c-kit+ cells which exhibit colony-forming ability in vitro and reconstruct the multilineage hematopoiesis of lethally irradiated recipient mice in vivo [3]. CD45+ liver side population (SP) cells, isolated based on Hoechst 33342 dye staining, are reported which have the potential of hematopoietic reconstitution and generate the lymphoid, myeloid, and erythroid lineages in the lethally irradiated recipient mice [4]. HSPCs were found in the adult human liver, and liver grafts after extensive perfusion can restore the recipient multilineage hematopoiesis to some extent [5,6,7].
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