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タイトル: | 3D osteogenic differentiation of human iPSCs reveals the role of TGFβ signal in the transition from progenitors to osteoblasts and osteoblasts to osteocytes |
著者: | Kawai, Shunsuke Sunaga, Junko Nagata, Sanae Nishio, Megumi Fukuda, Masayuki Kamakura, Takeshi Sun, Liping Jin, Yonghui https://orcid.org/0000-0002-7095-8295 (unconfirmed) Sakamoto, Satoko Watanabe, Akira Matsuda, Shuichi Adachi, Taiji https://orcid.org/0000-0001-5280-4156 (unconfirmed) Toguchida, Junya |
著者名の別形: | 川井, 俊介 須長, 純子 永田, 早苗 西尾, 恵 鎌倉, 武史 孫, 麗萍 金, 永輝 坂本, 智子 渡辺, 亮 松田, 秀一 安達, 泰治 戸口田, 淳也 |
キーワード: | Cell invasion Differentiation Growth factor signalling Multipotent stem cells Transcriptomics |
発行日: | 19-Jan-2023 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 13 |
論文番号: | 1094 |
抄録: | Although the formation of bone-like nodules is regarded as the differentiation process from stem cells to osteogenic cells, including osteoblasts and osteocytes, the precise biological events during nodule formation are unknown. Here we performed the osteogenic induction of human induced pluripotent stem cells using a three-dimensional (3D) culture system using type I collagen gel and a rapid induction method with retinoic acid. Confocal and time-lapse imaging revealed the osteogenic differentiation was initiated with vigorous focal proliferation followed by aggregation, from which cells invaded the gel. Invading cells changed their morphology and expressed osteocyte marker genes, suggesting the transition from osteoblasts to osteocytes. Single-cell RNA sequencing analysis revealed that 3D culture-induced cells with features of periosteal skeletal stem cells, some of which expressed TGFβ-regulated osteoblast-related molecules. The role of TGFβ signal was further analyzed in the transition from osteoblasts to osteocytes, which revealed that modulation of the TGFβ signal changed the morphology and motility of cells isolated from the 3D culture, suggesting that the TGFβ signal maintains the osteoblastic phenotype and the transition into osteocytes requires down-regulation of the TGFβ signal. |
著作権等: | © The Author(s) 2023 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. |
URI: | http://hdl.handle.net/2433/285067 |
DOI(出版社版): | 10.1038/s41598-023-27556-w |
PubMed ID: | 36658197 |
出現コレクション: | 学術雑誌掲載論文等 |
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