Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK
Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK
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DOI：
10.1101/gad.385606
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发表时间：
2006-08-01
影响因子：
10.5
通讯作者：
Jacobsen, Sten Eirik W.
中科院分区：
文献类型：
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作者：
Buza-Vidas, Natalija;Antonchuk, Jennifer;Jacobsen, Sten Eirik W.
细胞因子作为造血干细胞（HSC）扩增的调节剂的作用仍然是难以捉摸的。在此，我们确定血小板生成素（THPO）和细胞因子信号传导抑制剂LNK，作为对HSC扩增的生理调节剂。Lnk（-/-）HSC在产后继续扩张，到6个月龄时比正常值高出24倍。在干细胞区室内，这种扩增对自我更新的长期HSC（LT-HSC）具有高度选择性，其显示增强的THPO反应性。Lnk（-/-）HSC扩增依赖于THPO，12周龄Lnk（-/-）Thpo（-/-）小鼠的LT-HSC比Lnk（-/-）小鼠少65倍。在Lnk（-/-）小鼠中，多个髓系祖细胞而非淋巴系祖细胞的扩增也被证明是THPO依赖性的。
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.