Abstract
Hematopoietic stem cells (HSCs) give rise to variety of hematopoietic cells, and are responsible for blood production throughout adult life. Recent studies have demonstrated the potential of HSCs to produce various nonhematopoietic cells. Amplification of HSCs represents a potentially powerful approach not only to the treatment of various blood disorders but also to applying gene therapy or to regenerative medicine. Lnk is an adaptor protein consisting of PH, SH2 domains, and a C-terminal tyrosine phosphorylation site. Marked expansion of Blineage cells occurs in lnk-/- mice, indicating Lnk regulates B cell production by negatively controlling growth signals through c-Kit in B cell precursors. Lnk is also expressed in hematopoietic progenitors, and the number and the hematopoietic ability of HSCs are significantly increased in the absence of Lnk. While augmented signaling through c-Kit partly contributed to the increased progenitor cells in lnk-/- mice, it is likely that there exist Lnkdependent but c-Kit-independent signaling pathways whose absence leads to augmented ability of lnk-/- HSCs. These indicate that Lnk plays critical roles in the expansion and function of HSCs and provide useful clues for the amplification of HSCs and progenitor cells.
