zfh2 controls progenitor cell activation and differentiation in the adult Drosophila intestinal absorptive lineage.,PLOS Genetics

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zfh2 controls progenitor cell activation and differentiation in the adult Drosophila intestinal absorptive lineage.
PLOS Genetics ( IF 4.0 ) Pub Date : 2019-12-16 , DOI: 10.1371/journal.pgen.1008553
Sebastian E Rojas Villa ₁ , Fanju W Meng ₂ , Benoît Biteau ₂

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Many tissues rely on resident stem cell population to maintain homeostasis. The balance between cell proliferation and differentiation is critical to permit tissue regeneration and prevent dysplasia, particularly following tissue damage. Thus, understanding the cellular processes and genetic programs that coordinate these processes is essential. Here, we report that the conserved transcription factor zfh2 is specifically expressed in Drosophila adult intestinal stem cell and progenitors and is a critical regulator of cell differentiation in this lineage. We show that zfh2 expression is required and sufficient to drive the activation of enteroblasts, the non-proliferative progenitors of absorptive cells. This transition is characterized by the transient formation of thin membrane protrusions, morphological changes characteristic of migratory cells and compensatory stem cell proliferation. We found that zfh2 acts in parallel to insulin signaling and upstream of the TOR growth-promoting pathway during early differentiation. Finally, maintaining zfh2 expression in late enteroblasts blocks terminal differentiation and leads to the formation of highly dysplastic lesions, defining a new late cell differentiation transition. Together, our study greatly improves our understanding of the cascade of cellular changes and regulatory steps that control differentiation in the adult fly midgut and identifies zfh2 as a major player in these processes.

中文翻译：

zfh2控制成年果蝇肠道吸收谱系中祖细胞的活化和分化。

许多组织依靠常驻干细胞种群维持体内平衡。细胞增殖与分化之间的平衡对于允许组织再生和防止发育异常至关重要，特别是在组织损伤后。因此，了解细胞过程和协调这些过程的遗传程序至关重要。在这里，我们报告保守的转录因子zfh2在果蝇成年肠道干细胞和祖细胞中特异性表达，并且是该谱系中细胞分化的关键调节剂。我们显示zfh2表达是必需的，并且足以驱动成肠细胞（吸收性细胞的非增殖祖细胞）的激活。这种过渡的特征是瞬态形成的薄膜突起，迁移细胞的形态学变化特征和代偿性干细胞增殖。我们发现zfh2在早期分化过程中与胰岛素信号传导和TOR生长促进途径的上游平行发挥作用。最后，在晚期成肠细胞中维持zfh2表达可阻止终末分化，并导致高度增生性病变的形成，从而定义了新的晚期细胞分化过渡。在一起，我们的研究极大地增进了我们对细胞变化级联和控制成年蝇中肠分化的调控步骤的认识，并确定zfh2是这些过程的主要参与者。在晚期成肠细胞中维持zfh2表达可阻止终末分化并导致高度增生性病变的形成，从而定义了新的晚期细胞分化过渡。在一起，我们的研究极大地增进了我们对细胞变化级联和控制成年蝇中肠分化的调控步骤的认识，并确定zfh2是这些过程的主要参与者。在晚期成肠细胞中维持zfh2表达可阻止终末分化并导致高度增生性病变的形成，从而定义了新的晚期细胞分化过渡。在一起，我们的研究极大地增进了我们对细胞变化级联和控制成年蝇中肠分化的调控步骤的认识，并确定zfh2是这些过程的主要参与者。

更新日期：2019-12-17

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