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A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State
BACKGROUND: The scarcity of pluripotent stem cells poses a major challenge to the clinical application, given ethical and biosafety considerations. While germline stem cells commit to gamete differentiation throughout life, studies demonstrated the spontaneous acquisition of pluripotency by spermato...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693117/ https://www.ncbi.nlm.nih.gov/pubmed/38041111 http://dx.doi.org/10.1186/s13578-023-01150-z |
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author | Wei, Rui Zhang, Xiaoyu Li, Xiaoxiao Wen, Jian Liu, Hongyang Fu, Jiqiang Li, Li Zhang, Wenyi Liu, Zhen Yang, Yang Zou, Kang |
author_facet | Wei, Rui Zhang, Xiaoyu Li, Xiaoxiao Wen, Jian Liu, Hongyang Fu, Jiqiang Li, Li Zhang, Wenyi Liu, Zhen Yang, Yang Zou, Kang |
author_sort | Wei, Rui |
collection | PubMed |
description | BACKGROUND: The scarcity of pluripotent stem cells poses a major challenge to the clinical application, given ethical and biosafety considerations. While germline stem cells commit to gamete differentiation throughout life, studies demonstrated the spontaneous acquisition of pluripotency by spermatogonial stem cells (SSCs) from neonatal testes at a low frequency (1 in 1.5 × 10(7)). Notably, this process occurs without exogenous oncogenes or chemical supplementation. However, while knockout of the p53 gene accelerates the transformation of SSCs, it also increases risk and hampers their clinical use. RESULTS: We report a transformation system that efficiently and stably convert SSCs into pluripotent stem cells around 10 passages with the morphology similar to that of epiblast stem cells, which convert to embryonic stem (ES) cell-like colonies after change with ES medium. Epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast feeder (MEF) are essential for transformation, and addition of 2i (CHIR99021 and PD0325901) further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated the RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation. CONCLUSION: This system established an efficient and safe resource of pluripotent cells from autologous germline, and provide new avenues for regenerative medicine and animal cloning. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01150-z. |
format | Online Article Text |
id | pubmed-10693117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106931172023-12-03 A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State Wei, Rui Zhang, Xiaoyu Li, Xiaoxiao Wen, Jian Liu, Hongyang Fu, Jiqiang Li, Li Zhang, Wenyi Liu, Zhen Yang, Yang Zou, Kang Cell Biosci Research BACKGROUND: The scarcity of pluripotent stem cells poses a major challenge to the clinical application, given ethical and biosafety considerations. While germline stem cells commit to gamete differentiation throughout life, studies demonstrated the spontaneous acquisition of pluripotency by spermatogonial stem cells (SSCs) from neonatal testes at a low frequency (1 in 1.5 × 10(7)). Notably, this process occurs without exogenous oncogenes or chemical supplementation. However, while knockout of the p53 gene accelerates the transformation of SSCs, it also increases risk and hampers their clinical use. RESULTS: We report a transformation system that efficiently and stably convert SSCs into pluripotent stem cells around 10 passages with the morphology similar to that of epiblast stem cells, which convert to embryonic stem (ES) cell-like colonies after change with ES medium. Epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast feeder (MEF) are essential for transformation, and addition of 2i (CHIR99021 and PD0325901) further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated the RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation. CONCLUSION: This system established an efficient and safe resource of pluripotent cells from autologous germline, and provide new avenues for regenerative medicine and animal cloning. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01150-z. BioMed Central 2023-12-01 /pmc/articles/PMC10693117/ /pubmed/38041111 http://dx.doi.org/10.1186/s13578-023-01150-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wei, Rui Zhang, Xiaoyu Li, Xiaoxiao Wen, Jian Liu, Hongyang Fu, Jiqiang Li, Li Zhang, Wenyi Liu, Zhen Yang, Yang Zou, Kang A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title | A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title_full | A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title_fullStr | A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title_full_unstemmed | A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title_short | A rapid and stable spontaneous reprogramming system of Spermatogonial stem cells to Pluripotent State |
title_sort | rapid and stable spontaneous reprogramming system of spermatogonial stem cells to pluripotent state |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693117/ https://www.ncbi.nlm.nih.gov/pubmed/38041111 http://dx.doi.org/10.1186/s13578-023-01150-z |
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