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一种用于研究集体细胞迁移对诱导多能干细胞集落内空间自组织影响的体外培养平台。

An in vitro culture platform for studying the effect of collective cell migration on spatial self-organization within induced pluripotent stem cell colonies.

作者信息

Kim Mee-Hae, Kuroda Masaki, Ke Ding, Thanuthanakhun Naruchit, Kino-Oka Masahiro

机构信息

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Research Base for Cell Manufacturability, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.

出版信息

J Biol Eng. 2023 Mar 30;17(1):25. doi: 10.1186/s13036-023-00341-z.

DOI:10.1186/s13036-023-00341-z
PMID:36998087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10064534/
Abstract

BACKGROUND

Human induced pluripotent stem cells (hiPSCs) provide an in vitro system to identify the impact of cell behavior on the earliest stages of cell fate specification during human development. Here, we developed an hiPSC-based model to study the effect of collective cell migration in meso-endodermal lineage segregation and cell fate decisions through the control of space confinement using a detachable ring culture system.

RESULTS

The actomyosin organization of cells at the edge of undifferentiated colonies formed in a ring barrier differed from that of the cells in the center of the colony. In addition, even in the absence of exogenous supplements, ectoderm, mesoderm, endoderm, and extraembryonic cells differentiated following the induction of collective cell migration at the colony edge by removing the ring-barrier. However, when collective cell migration was inhibited by blocking E-cadherin function, this fate decision within an hiPSC colony was altered to an ectodermal fate. Furthermore, the induction of collective cell migration at the colony edge using an endodermal induction media enhanced endodermal differentiation efficiency in association with cadherin switching, which is involved in the epithelial-mesenchymal transition.

CONCLUSIONS

Our findings suggest that collective cell migration can be an effective way to drive the segregation of mesoderm and endoderm lineages, and cell fate decisions of hiPSCs.

摘要

背景

人类诱导多能干细胞（hiPSC）提供了一个体外系统，用于确定细胞行为对人类发育过程中细胞命运决定最早阶段的影响。在此，我们开发了一种基于hiPSC的模型，通过使用可拆卸环培养系统控制空间限制，来研究集体细胞迁移在中胚层-内胚层谱系分离和细胞命运决定中的作用。

结果

在环形屏障中形成的未分化集落边缘的细胞，其肌动球蛋白组织与集落中心的细胞不同。此外，即使在没有外源补充剂的情况下，通过移除环形屏障诱导集落边缘的集体细胞迁移后，外胚层、中胚层、内胚层和胚外细胞也会分化。然而，当通过阻断E-钙黏蛋白功能抑制集体细胞迁移时，hiPSC集落内的这种命运决定会改变为外胚层命运。此外，使用内胚层诱导培养基在集落边缘诱导集体细胞迁移，与参与上皮-间质转化的钙黏蛋白转换相关，提高了内胚层分化效率。

结论

我们的研究结果表明，集体细胞迁移可能是驱动中胚层和内胚层谱系分离以及hiPSC细胞命运决定的有效方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/441592e163cb/13036_2023_341_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/478d184c4a9e/13036_2023_341_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/26f287dce40b/13036_2023_341_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/56feafef52ad/13036_2023_341_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/91439178d810/13036_2023_341_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/b8c8db18abdd/13036_2023_341_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/7f97549f3226/13036_2023_341_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/441592e163cb/13036_2023_341_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/478d184c4a9e/13036_2023_341_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/26f287dce40b/13036_2023_341_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/56feafef52ad/13036_2023_341_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/91439178d810/13036_2023_341_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/b8c8db18abdd/13036_2023_341_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/7f97549f3226/13036_2023_341_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f9f/10064534/441592e163cb/13036_2023_341_Fig7_HTML.jpg

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本文引用的文献

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