关键词: AMPs DPP Drosophila ISCs Midgut Rab11

Mesh : Animals Cell Differentiation / genetics Drosophila Proteins / metabolism genetics rab GTP-Binding Proteins / metabolism genetics Signal Transduction Larva / growth & development metabolism genetics Cell Proliferation Stem Cells / metabolism cytology Drosophila melanogaster / metabolism genetics growth & development Stem Cell Niche

来  源:   DOI:10.1016/j.yexcr.2024.114092

Abstract:
Asymmetric stem cell divisions play instrumental roles in the maintenance, growth and differentiation of organs. Failure of asymmetric stem cell divisions may result in an array of developmental disorders, including cancer. It is well established that the gene, inscuteable, acts as the upstream component of asymmetric cell divisions. In Drosophila larval midgut, a founder adult midgut precursor (AMP) experiences an asymmetric division to instruct its first daughter to become a peripheral cell that serves as a niche where the AMP and its future daughters can remain undifferentiated. The present study demonstrates that inscuteable expressing stem cells require Rab11, a conserved small Ras-like GTPase, for proper proliferation and differentiation. As insc-GAL4 mediated Rab11RNAi in Drosophila larval and adult midguts show the disruption of the niche microenvironment of adult midgut precursors as well as elevated DPP signalling at the larval stage, which is associated with aberrant over-proliferation and early differentiation of larval AMPs and adult intestinal stem cells. The observed connections between Rab11, larval AMP proliferation, niche establishment, and DPP signalling highlight the potential for Rab11 to serve as a key regulatory factor in maintaining tissue homeostasis and balanced cellular growth.
摘要:
不对称干细胞分裂在维持中起着重要作用,器官的生长和分化。不对称干细胞分裂失败可能导致一系列发育障碍,包括癌症.众所周知,这种基因,贪恋,作为不对称细胞分裂的上游组件。在果蝇幼虫中肠中,创始人成年中肠前体(AMP)经历了不对称分裂,以指示其第一个女儿成为外周细胞,该细胞充当AMP及其未来女儿可以保持未分化的利基。本研究表明,可表达干细胞需要Rab11,一种保守的小Ras样GTP酶,适当的增殖和分化。由于insc-GAL4在果蝇幼虫和成年中肠中介导的Rab11RNAi显示出成年中肠前体的生态位微环境的破坏以及在幼虫阶段DPP信号的升高,这与幼虫AMPs(成年中肠祖细胞)和成年肠干细胞的异常过度增殖和早期分化有关。观察到的Rab11,幼虫AMP增殖之间的连接,利基建立,和DPP信号强调了Rab11作为维持组织稳态和平衡细胞生长的关键调节因子的潜力。
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