Tamamouna Vasilia, Panagi Myrofora, Theophanous Andria, Demosthenous Maria, Michail Maria, Papadopoulou Markella, Teloni Savvas, Pitsouli Chrysoula, Apidianakis Yiorgos
Department of Biological Sciences, University of Cyprus, 2109 Nicosia, Cyprus.
Department of Biological Sciences, University of Cyprus, 2109 Nicosia, Cyprus
Development. 2020 Jun 8;147(11):dev189472. doi: 10.1242/dev.189472.
Systemic and stem cell niche-emanating cytokines and growth factors can promote regeneration, through mitosis. High mitosis, however, predisposes for all types of cancer and, thus, a trade-off exists between regeneration capacity and tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative signaling in stem cell mitosis of adult midgut of different genetic backgrounds. We provide evidence of two naturally occurring types of balance between mitosis and enterocyte nucleus growth: one based mostly on stem cell mitosis producing new cells and the other based mostly on the degree of young enterocyte nucleus size increase. Mitosis promotes intestinal host defense to infection, but predisposes for dysplasia in the form of stem cell-like clusters. Enterocyte nucleus growth also promotes host defense, without the drawback of promoting dysplasia. Through quantitative genetics, we identified as an autocrine and paracrine inducer of stem cell mitosis. expression in immature epithelial cells tilts the balance towards mitosis and dysplasia via a positive-feedback loop of highly mitotic stem cells sustaining more small nucleus enterocytes, which in turn supply more Eiger.
全身和干细胞微环境产生的细胞因子及生长因子可通过有丝分裂促进再生。然而，高有丝分裂率易引发各类癌症，因此在再生能力与组织稳态之间存在权衡。在此，我们研究不同遗传背景的成年中肠干细胞有丝分裂中组织内在再生信号的作用。我们提供了有丝分裂与肠上皮细胞核生长之间两种自然存在的平衡类型的证据：一种主要基于干细胞有丝分裂产生新细胞，另一种主要基于年轻肠上皮细胞核大小增加的程度。有丝分裂促进肠道对感染的宿主防御，但易引发干细胞样簇形式的发育异常。肠上皮细胞核生长也促进宿主防御，且不存在促进发育异常的弊端。通过数量遗传学，我们鉴定出[具体物质]作为干细胞有丝分裂的自分泌和旁分泌诱导剂。[具体物质]在未成熟上皮细胞中的表达通过高有丝分裂干细胞维持更多小核肠上皮细胞的正反馈回路，使平衡倾向于有丝分裂和发育异常，而这些小核肠上皮细胞又反过来提供更多[具体物质]。
