Prickle1-driven basement membrane deposition of the iPSC-derived embryoid bodies is separable from the establishment of apicobasal polarity
Prickle1-driven basement membrane deposition of the iPSC-derived embryoid bodies is separable from the establishment of apicobasal polarity
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DOI：
10.1111/cpr.13595
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发表时间：
2024-01-07
影响因子：
8.5
通讯作者：
Liu，Chunqiao
中科院分区：
文献类型：
--
作者：
Guo，Dianlei;Liu，Sikai;Liu，Chunqiao
基底膜（BM）成分的沉积与细胞极性的建立密切相关。之前，我们表明 Prickle1 对于泪管伸长中的 BM 沉积和细胞极性事件至关重要。为了更深入地了解 BM 形成和细胞极性之间的密切关系，我们生成了诱导多能干细胞 (iPSC) 衍生的胚状体 (EB)，其基底膜分隔内脏内胚层 (VE) 和内部 EB 细胞团。我们发现Prickle1在正常EB的VE中高表达，而Prickle1突变的EB表现出严重受损的BM。值得注意的是，基底膜的形成似乎依赖于 VE 细胞的适当微管网络，而该网络在 Prickle1 突变 EB 中被破坏。此外，VE 中囊泡运输的破坏阻碍了 BM 的分泌。此外，在突变 EB 中重新引入 Prickle1 可以完全挽救 BM 形成，但不能挽救 VE 的顶端基底细胞极性。我们的数据与其他人的研究相结合，强调了即使在缺乏已建立的通用极性机制的情况下，Prickle1 在胚胎胚层分化过程中指导 VE 细胞 BM 成分分泌中的保守作用。我们的研究介绍了一种基于 iPSC 衍生的 EB 的新型系统，用于研究与细胞极性相关的细胞和分子事件。
Basement membrane (BM) component deposition is closely linked to the establishment of cell polarity. Previously, we showed that Prickle1 is crucial for BM deposition and cell polarity events in tear duct elongation. To gain a deeper understanding of the intimate relationship between BM formation and cell polarity, we generated induced pluripotent stem cells (iPSCs)‐derived embryoid bodies (EBs) with a basement membrane separating the visceral endoderm (VE) and inner EB cell mass. We found thatPrickle1was highly expressed in VE of the normal EBs, and thePrickle1mutant EBs displayed severely impaired BM. Notably, the formation of the basement membrane appeared to rely on the proper microtubule network of the VE cells, which was disrupted in thePrickle1mutant EBs. Moreover, disruption of vesicle trafficking in the VE hindered BM secretion. Furthermore, reintroducing Prickle1 in the mutant EBs completely rescued BM formation but not the apicobasal cell polarity of the VE. Our data, in conjunction with studies by others, highlight the conserved role of Prickle1 in directing the secretion of BM components of the VE cells during embryonic germ layer differentiation, even in the absence of established general polarity machinery. Our study introduces a novel system based on iPSCs‐derived EBs for investigating cellular and molecular events associated with cell polarity.