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干细胞多能性的分泌蛋白质组特征。

A secreted proteomic footprint for stem cell pluripotency.

机构信息

Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.

Biodiscovery Institute, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, University Park, Nottingham, United Kingdom.

出版信息

PLoS One. 2024 Jun 14;19(6):e0299365. doi: 10.1371/journal.pone.0299365. eCollection 2024.

DOI:10.1371/journal.pone.0299365
PMID:38875182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11178176/
Abstract

With a view to developing a much-needed non-invasive method for monitoring the healthy pluripotent state of human stem cells in culture, we undertook proteomic analysis of the waste medium from cultured embryonic (Man-13) and induced (Rebl.PAT) human pluripotent stem cells (hPSCs). Cells were grown in E8 medium to maintain pluripotency, and then transferred to FGF2 and TGFβ deficient E6 media for 48 hours to replicate an early, undirected dissolution of pluripotency. We identified a distinct proteomic footprint associated with early loss of pluripotency in both hPSC lines, and a strong correlation with changes in the transcriptome. We demonstrate that multiplexing of four E8- against four E6- enriched secretome biomarkers provides a robust, diagnostic metric for the pluripotent state. These biomarkers were further confirmed by Western blotting which demonstrated consistent correlation with the pluripotent state across cell lines, and in response to a recovery assay.

摘要

为了开发一种急需的非侵入性方法来监测培养中的人类多能干细胞的健康多能状态，我们对培养的胚胎（Man-13）和诱导（Rebl.PAT）人类多能干细胞（hPSC）的废培养基进行了蛋白质组学分析。细胞在 E8 培养基中生长以维持多能性，然后转移到缺乏 FGF2 和 TGFβ 的 E6 培养基中 48 小时，以复制早期无定向的多能性溶解。我们在两种 hPSC 系中都鉴定到与早期多能性丧失相关的独特蛋白质组学特征，并且与转录组的变化具有很强的相关性。我们证明，将四个 E8-与四个 E6-富集的分泌组生物标志物进行多重分析，可以为多能状态提供一种强大的诊断指标。这些生物标志物通过 Western blot 进一步得到了验证，Western blot 显示在细胞系之间以及对恢复测定的反应中，与多能状态具有一致的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/9c0ba569dadc/pone.0299365.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/eba47fdbae5b/pone.0299365.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/4e25897dea4a/pone.0299365.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/04a95123ee85/pone.0299365.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/d667a7626c82/pone.0299365.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/544aad40da15/pone.0299365.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/b2d02c787a03/pone.0299365.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/9c0ba569dadc/pone.0299365.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/eba47fdbae5b/pone.0299365.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/4e25897dea4a/pone.0299365.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/04a95123ee85/pone.0299365.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/d667a7626c82/pone.0299365.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/544aad40da15/pone.0299365.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/b2d02c787a03/pone.0299365.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ea/11178176/9c0ba569dadc/pone.0299365.g007.jpg

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引用本文的文献

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Correction: A secreted proteomic footprint for stem cell pluripotency.更正：干细胞多能性的一种分泌蛋白质组印记
PLoS One. 2025 Jan 2;20(1):e0317156. doi: 10.1371/journal.pone.0317156. eCollection 2025.

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