Stier Sebastian, Cheng Tao, Dombkowski David, Carlesso Nadia, Scadden David T
Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA.
Blood. 2002 Apr 1;99(7):2369-78. doi: 10.1182/blood.v99.7.2369.
Hematopoietic stem cells sequentially pass through a series of decision points affecting self-renewal or lineage-specific differentiation. Notch1 receptor is a known modulator of lineage-specific events in hematopoiesis that we assessed in the context of in vivo stem cell kinetics. Using RAG-1(-/-) mouse stems cells, we documented increased stem cell numbers due to decreased differentiation and enhanced stem cell self-renewal induced by Notch1. Unexpectedly, preferential lymphoid over myeloid lineage commitment was noted when differentiation occurred. Therefore, Notch1 affects 2 decision points in stem cell regulation, favoring self-renewal over differentiation and lymphoid over myeloid lineage outcome. Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome.
造血干细胞依次通过一系列影响自我更新或谱系特异性分化的决策点。Notch1受体是造血过程中已知的谱系特异性事件调节因子，我们在体内干细胞动力学背景下对其进行了评估。利用RAG-1(-/-)小鼠干细胞，我们记录到由于Notch1诱导的分化减少和干细胞自我更新增强，干细胞数量增加。出乎意料的是，分化发生时，观察到淋巴谱系相对于髓系谱系的优先定向。因此，Notch1影响干细胞调节中的两个决策点，有利于自我更新而非分化，以及淋巴谱系而非髓系谱系的结果。Notch1为干细胞操纵策略提供了一个有吸引力的靶点，特别是在免疫缺陷和获得性免疫缺陷综合征的背景下。
