CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells
CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells
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DOI：
10.1073/pnas.1215438110
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发表时间：
2013-04-02
影响因子：
11.1
通讯作者：
Waskow, Claudia
中科院分区：
文献类型：
--
作者：
Arndt, Kathrin;Grinenko, Tatyana;Waskow, Claudia
五跨膜糖蛋白CD 133在多种体干细胞的细胞表面表达，并且其被广泛用作分离和表征人造血干细胞（HSC）和癌症干细胞的细胞表面标志物。CD 133在细胞生物学基础上与人HSC中的干细胞命运决定相关，并作为干细胞维持和扩增的重要生理调节因子出现。然而，其在小鼠造血系统中的表达和生理相关性是难以捉摸的。我们在这里表明，CD 133是由骨髓驻留的小鼠造血干细胞和髓样前体细胞的发展倾向，产生粒细胞和单核细胞的表达。然而，在稳态造血过程中和移植后，CD 133对HSC池的大小和功能是不利的，表明小鼠和人之间存在实质性的种属差异。但是，在此情况下，CD 133似乎是生长发育的修饰剂-稳态下骨髓中的因子反应性骨髓红细胞前体细胞和造血应激后的成熟红细胞。总之，这些研究表明，CD 133不是小鼠造血干细胞功能的关键调节因子，但它在稳态期间和体内骨髓毒性应激后改变生长因子应答性造血祖细胞的频率。
Pentatransmembrane glycoprotein prominin-1 (CD133) is expressed at the cell surface of multiple somatic stem cells, and it is widely used as a cell surface marker for the isolation and characterization of human hematopoietic stem cells (HSCs) and cancer stem cells. CD133 has been linked on a cell biological basis to stem cell-fate decisions in human HSCs and emerges as an important physiological regulator of stem cell maintenance and expansion. Its expression and physiological relevance in the murine hematopoietic system is nevertheless elusive. We show here that CD133 is expressed by bone marrow-resident murine HSCs and myeloid precursor cells with the developmental propensity to give rise to granulocytes and monocytes. However, CD133 is dispensable for the pool size and function of HSCs during steady-state hematopoiesis and after transplantation, demonstrating a substantial species difference between mouse and man. Blood cell numbers in the periphery are normal; however, CD133 appears to be a modifier for the development of growth-factor responsive myeloerythroid precursor cells in the bone marrow under steady state and mature red blood cells after hematopoietic stress. Taken together, these studies show that CD133 is not a critical regulator of hematopoietic stem cell function in mouse but that it modifies frequencies of growth-factor responsive hematopoietic progenitor cells during steady state and after myelotoxic stress in vivo.