Apical-basal polarity precisely determines intestinal stem cell number by regulating Prospero threshold
Apical-basal polarity precisely determines intestinal stem cell number by regulating Prospero threshold
复制标题
顶端-基底极性通过调节Prospero阈值精确决定肠道干细胞数量
DOI：
10.1016/j.celrep.2023.112093
复制
发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Zheng Guo
中科院分区：
文献类型：
--
作者：
Song Wu;Yang Yang;Ruizhi Tang;Song Zhang;Peizhong Qin;Rong Lin;Neus Rafel;Elena M Lucchetta;Benjamin Ohlstein;Zheng Guo
顶基极性和细胞命运决定因素对细胞命运和干细胞数量的控制至关重要。然而，它们之间的相互作用导致精确的干细胞数量仍然不清楚。果蝇蛹肠干细胞（pISCs）不对称分裂，产生一个顶端ISC祖细胞和一个基底Prospero（Pros）+肠内分泌母细胞（EMC），随后在成年之前每个子细胞对称分裂，为研究极性丧失的结果提供了理想的系统。使用谱系追踪和离体活体成像，我们确定了一个精确确定ISC数量的互锁极性调节网络：Bazooka通过激活Notch信号传导抑制Pros积累，以维持pISC顶端子代中的干细胞命运。Pros的阈值促进向EMCs的分化并避免ISC样细胞命运，并且Pros的过阈值抑制米兰达表达以确保pISC基底子代中的对称分裂。我们的工作表明，分化因子的极性依赖性阈值精确地控制干细胞数量。
Apical-basal polarity and cell-fate determinants are crucial for the cell fate and control of stem cell numbers. However, their interplay leading to a precise stem cell number remains unclear. Drosophila pupal intestinal stem cells (pISCs) asymmetrically divide, generating one apical ISC progenitor and one basal Prospero (Pros)+ enteroendocrine mother cell (EMC), followed by symmetric divisions of each daughter before adulthood, providing an ideal system to investigate the outcomes of polarity loss. Using lineage tracing and ex vivo live imaging, we identify an interlocked polarity regulation network precisely determining ISC number: Bazooka inhibits Pros accumulation by activating Notch signaling to maintain stem cell fate in pISC apical daughters. A threshold of Pros promotes differentiation to EMCs and avoids ISC-like cell fate, and over-threshold of Pros inhibits miranda expression to ensure symmetric divisions in pISC basal daughters. Our work suggests that a polarity-dependent threshold of a differentiation factor precisely controls stem cell number.