Somatic support cells restrict germline stem cell self-renewal and promote differentiation

Somatic support cells restrict germline stem cell self-renewal and promote differentiation
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DOI:
10.1038/35037606
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发表时间:
2000-10-12
期刊:
影响因子:
64.8
通讯作者:
Fuller, MT
Fuller, MT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kiger, AA;White-Cooper, H;Fuller, MT

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干细胞在整个成人生活中维持高度分化,寿命短的细胞类型,包括血液,皮肤和精子(1)。了解调节干细胞行为的机制对于实现其在再生医学中的潜力至关重要(2)。干细胞的一个基本特征是它们的不对称分裂能力:子细胞保留干细胞身份或启动分化。然而,干细胞也能够对称分裂,其中两个子细胞都保持干细胞(3-6),这表明必须存在平衡自我更新能力与分化的机制。在这里,我们提出的证据表明,支持细胞周围的干细胞限制自我更新和控制干细胞的数量,确保不对称分裂。果蝇表皮生长因子受体在体细胞中的功能丧失破坏了雄性生殖系中自我更新与分化的平衡,增加了生殖系干细胞的数量。我们建议,这种受体的激活指定体细胞支持细胞的正常行为,反过来,体细胞发挥监护人的作用,提供信息,防止自我更新的干细胞身份的生殖细胞,他们包围。
Stem cells maintain populations of highly differentiated, short-lived cell-types, including blood, skin and sperm, throughout adult life(1). Understanding the mechanisms that regulate stem cell behaviour is crucial for realizing their potential in regenerative medicine(2). A fundamental characteristic of stem cells is their capacity for asymmetric division: daughter cells either retain stem cell identity or initiate differentiation. However, stem cells are also capable of symmetric division where both daughters remain stem cells(3-6), indicating that mechanisms must exist to balance self-renewal capacity with differentiation. Here we present evidence that support cells surrounding the stem cells restrict self-renewal and control stem cell number by ensuring asymmetric division. Loss of function of the Drosophila Epidermal growth factor receptor in somatic cells disrupted the balance of self-renewal versus differentiation in the male germline, increasing the number of germline stem cells. We propose that activation of this receptor specifies normal behaviour of somatic support cells; in turn, the somatic cells play a guardian role, providing information that prevents self-renewal of stem cell identity by the germ cell they enclose.