Buza-Vidas Natalija, Antonchuk Jennifer, Qian Hong, Månsson Robert, Luc Sidinh, Zandi Sasan, Anderson Kristina, Takaki Satoshi, Nygren Jens M, Jensen Christina T, Jacobsen Sten Eirik W
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden.
Genes Dev. 2006 Aug 1;20(15):2018-23. doi: 10.1101/gad.385606.
The role of cytokines as regulators of hematopoietic stem cell (HSC) expansion remains elusive. Herein, we identify thrombopoietin (THPO) and the cytokine signaling inhibitor LNK, as opposing physiological regulators of HSC expansion. Lnk(-/-) HSCs continue to expand postnatally, up to 24-fold above normal by 6 mo of age. Within the stem cell compartment, this expansion is highly selective for self-renewing long-term HSCs (LT-HSCs), which show enhanced THPO responsiveness. Lnk(-/-) HSC expansion is dependent on THPO, and 12-wk-old Lnk(-/-)Thpo(-/-) mice have 65-fold fewer LT-HSCs than Lnk(-/-) mice. Expansions of multiple myeloid, but not lymphoid, progenitors in Lnk(-/-) mice also proved THPO-dependent.
细胞因子作为造血干细胞(HSC)扩增调节因子的作用仍不清楚。在此,我们确定血小板生成素(THPO)和细胞因子信号转导抑制剂LNK是HSC扩增的相反生理调节因子。Lnk基因敲除(Lnk-/-)的造血干细胞在出生后持续扩增,到6月龄时比正常水平高出24倍。在干细胞区室中,这种扩增对自我更新的长期造血干细胞(LT-HSC)具有高度选择性,这些细胞对THPO的反应性增强。Lnk-/-造血干细胞的扩增依赖于THPO,12周龄的Lnk-/-Thpo-/-小鼠的LT-HSC比Lnk-/-小鼠少65倍。Lnk-/-小鼠中多个髓系祖细胞(而非淋巴系祖细胞)的扩增也证明依赖于THPO。