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Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes

BACKGROUND: Salivary glands produce saliva that play essential roles in digestion and oral health. Derivation of salivary gland organoids from pluripotent stem cells (PSCs) provides a powerful platform to model the organogenesis processes during development. A few studies attempted to differentiate...

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Autores principales: Zhang, Siqi, Sui, Yi, Yan, Shuang, Zhang, Yifei, Ding, Chong, Su, Xiaodong, Xiong, Jingwei, Wei, Shicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330698/
https://www.ncbi.nlm.nih.gov/pubmed/35902913
http://dx.doi.org/10.1186/s13287-022-03033-5
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author Zhang, Siqi
Sui, Yi
Yan, Shuang
Zhang, Yifei
Ding, Chong
Su, Xiaodong
Xiong, Jingwei
Wei, Shicheng
author_facet Zhang, Siqi
Sui, Yi
Yan, Shuang
Zhang, Yifei
Ding, Chong
Su, Xiaodong
Xiong, Jingwei
Wei, Shicheng
author_sort Zhang, Siqi
collection PubMed
description BACKGROUND: Salivary glands produce saliva that play essential roles in digestion and oral health. Derivation of salivary gland organoids from pluripotent stem cells (PSCs) provides a powerful platform to model the organogenesis processes during development. A few studies attempted to differentiate PSCs into salivary gland organoids. However, none of them could recapitulate the morphogenesis of the embryonic salivary glands, and most of the protocols involved complicated manufacturing processes. METHODS: To generate PSC-derived salivary gland placodes, the mouse embryonic stem cells were first differentiated into oral ectoderm by treatment with BMP4 on day 3. Retinoic acid and bFGF were then applied to the cultures from day 4 to day 6, followed by a 4-day treatment of FGF10. The PSC-derived salivary gland placodes on day 10 were transplanted to kidney capsules to determine the regenerative potential. Quantitative reverse transcriptase–polymerase chain reaction, immunofluorescence, and RNA-sequencing were performed to identify the PSC-derived SG placodes. RESULTS: We showed that step-wise treatment of retinoic acid and FGF10 promoted the differentiation of PSCs into salivary gland placodes, which can recapitulate the early morphogenetic events of their fetal counterparts, including the thickening, invagination, and then formed initial buds. The PSC-derived salivary gland placodes also differentiated into developing duct structures and could develop to striated and excretory ducts when transplanted in vivo. CONCLUSIONS: The present study provided an easy and safe method to generate salivary gland placodes from PSCs, which offered possibilities for studying salivary gland development in vitro and developing new cell therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03033-5.
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spelling pubmed-93306982022-07-29 Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes Zhang, Siqi Sui, Yi Yan, Shuang Zhang, Yifei Ding, Chong Su, Xiaodong Xiong, Jingwei Wei, Shicheng Stem Cell Res Ther Research BACKGROUND: Salivary glands produce saliva that play essential roles in digestion and oral health. Derivation of salivary gland organoids from pluripotent stem cells (PSCs) provides a powerful platform to model the organogenesis processes during development. A few studies attempted to differentiate PSCs into salivary gland organoids. However, none of them could recapitulate the morphogenesis of the embryonic salivary glands, and most of the protocols involved complicated manufacturing processes. METHODS: To generate PSC-derived salivary gland placodes, the mouse embryonic stem cells were first differentiated into oral ectoderm by treatment with BMP4 on day 3. Retinoic acid and bFGF were then applied to the cultures from day 4 to day 6, followed by a 4-day treatment of FGF10. The PSC-derived salivary gland placodes on day 10 were transplanted to kidney capsules to determine the regenerative potential. Quantitative reverse transcriptase–polymerase chain reaction, immunofluorescence, and RNA-sequencing were performed to identify the PSC-derived SG placodes. RESULTS: We showed that step-wise treatment of retinoic acid and FGF10 promoted the differentiation of PSCs into salivary gland placodes, which can recapitulate the early morphogenetic events of their fetal counterparts, including the thickening, invagination, and then formed initial buds. The PSC-derived salivary gland placodes also differentiated into developing duct structures and could develop to striated and excretory ducts when transplanted in vivo. CONCLUSIONS: The present study provided an easy and safe method to generate salivary gland placodes from PSCs, which offered possibilities for studying salivary gland development in vitro and developing new cell therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03033-5. BioMed Central 2022-07-28 /pmc/articles/PMC9330698/ /pubmed/35902913 http://dx.doi.org/10.1186/s13287-022-03033-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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
Zhang, Siqi
Sui, Yi
Yan, Shuang
Zhang, Yifei
Ding, Chong
Su, Xiaodong
Xiong, Jingwei
Wei, Shicheng
Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title_full Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title_fullStr Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title_full_unstemmed Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title_short Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
title_sort retinoic acid and fgf10 promote the differentiation of pluripotent stem cells into salivary gland placodes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330698/
https://www.ncbi.nlm.nih.gov/pubmed/35902913
http://dx.doi.org/10.1186/s13287-022-03033-5
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