XXXX in megakaryocytes is critical for maintenance of hematopoietic stem cells in the bone marrow.

@entity73346 @entity19 @entity73347 @entity26511 @entity19181 @entity61049
UNASSIGNED: Hematopoietic stem cells (HSCs) depend on the bone marrow (BM) niche for their maintenance, proliferation, and differentiation. The BM niche is composed of nonhematopoietic and mature hematopoietic cells, including megakaryocytes (Mks). @entity19181 ( @entity19181 ) is a crucial cytokine produced by BM niche cells. However, the cellular source of @entity19181 , upon which HSCs primarily depend, is unclear. Moreover, no specific molecular pathway for the regulation of @entity19181 production in the BM has been identified. Here, we demonstrate that the membrane protein @entity61049 ( @entity61049 ) mediates the production of @entity19181 and other factors in Mks. @entity19 conditionally deleted for @entity61049 in Mks ( @entity61049 (Mk  /  )) produced lower levels of @entity19181 in Mks. @entity61049 -deficient Mks showed down-regulation of @entity61049 -related signaling molecules @entity26511 , @entity73346 , and @entity73347 . Knockdown of these molecules in cultured Mks decreased expression of @entity19181 . @entity61049 (Mk  /  ) @entity19 exhibited reduced BM HSC quiescence and repopulation potential, along with extramedullary hematopoiesis. The low level of @entity19181 production may account for the decline in HSC potential in @entity61049 (Mk  /  ) @entity19 , as administration of recombinant @entity19181 to @entity61049 (Mk  /  ) @entity19 restored stem cell potential. Our study identifies @entity61049 signaling as a novel molecular mechanism mediating the production of @entity19181 and other factors for the maintenance of HSCs.
