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タイトル: | A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility |
著者: | Chen, Si Jing Hashimoto, Kazuya Fujio, Kosuke Hayashi, Karin Paul, Sudip Kumar Yuzuriha, Akinori Qiu, Wei-Yin Nakamura, Emiri Kanashiro, Maria Alejandra Kabata, Mio Nakamura, Sou Sugimoto, Naoshi https://orcid.org/0000-0002-7271-9175 (unconfirmed) Kaneda, Atsushi Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Saito, Hirohide Takayama, Naoya Eto, Koji https://orcid.org/0000-0002-5863-7122 (unconfirmed) |
著者名の別形: | 陳, 思婧 林, 香倫 杠 明憲 中村, 壮 杉本, 直志 山本, 拓也 齊藤, 博英 高山, 直也 江藤, 浩之 |
キーワード: | Biotechnology Platelets Pluripotent stem cells |
発行日: | 22-Mar-2024 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 15 |
論文番号: | 2588 |
抄録: | We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population. |
記述: | iPS細胞由来血小板造血における免疫巨核球の制御機構の発見 血小板の大量製造に向けた巨核球マスターセルの品質管理に応用可能. 京都大学プレスリリース. 2024-03-26. Discovering a new microRNA-regulated pathway to boost iPS cell-derived platelet production. 京都大学プレスリリース. 2024-03-26. |
著作権等: | © The Author(s) 2024 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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/2433/287580 |
DOI(出版社版): | 10.1038/s41467-024-46605-0 |
PubMed ID: | 38519457 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/240326-110000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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