Kiger A A, White-Cooper H, Fuller M T
Department of Developmental Biology, Stanford University School of Medicine, California 94305-5329, USA.
Nature. 2000 Oct 12;407(6805):750-4. doi: 10.1038/35037606.
Stem cells maintain populations of highly differentiated, short-lived cell-types, including blood, skin and sperm, throughout adult life. Understanding the mechanisms that regulate stem cell behaviour is crucial for realizing their potential in regenerative medicine. 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, 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.
在整个成年期，干细胞维持着包括血液、皮肤和精子在内的高度分化、寿命短暂的细胞类型群体。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。干细胞的一个基本特征是它们的不对称分裂能力：子细胞要么保留干细胞身份，要么开始分化。然而，干细胞也能够进行对称分裂，即两个子细胞都保持为干细胞，这表明必须存在一些机制来平衡自我更新能力和分化。在这里，我们提供证据表明，干细胞周围的支持细胞通过确保不对称分裂来限制自我更新并控制干细胞数量。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数量。我们提出，该受体的激活决定了体细胞支持细胞的正常行为；反过来，体细胞发挥着守护者的作用，提供信息以防止它们所包围的生殖细胞自我更新干细胞身份。
