Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes
Abstract 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 differ...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-03033-5 |
| _version_ | 1828374458709049344 |
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| author | Siqi Zhang Yi Sui Shuang Yan Yifei Zhang Chong Ding Xiaodong Su Jingwei Xiong Shicheng Wei |
| author_facet | Siqi Zhang Yi Sui Shuang Yan Yifei Zhang Chong Ding Xiaodong Su Jingwei Xiong Shicheng Wei |
| author_sort | Siqi Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-14T07:33:10Z |
| format | Article |
| id | doaj.art-9ee91df5651946f3a17aba58e142cacc |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-14T07:33:10Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-9ee91df5651946f3a17aba58e142cacc2022-12-22T02:05:47ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111310.1186/s13287-022-03033-5Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodesSiqi Zhang0Yi Sui1Shuang Yan2Yifei Zhang3Chong Ding4Xiaodong Su5Jingwei Xiong6Shicheng Wei7Central Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityCentral Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityCentral Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityCentral Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityCentral Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityBiomedical Pioneering Innovation Center (BIOPIC) State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking UniversityInstitute of Molecular Medicine, Peking UniversityCentral Laboratory, and Department of Oral and Maxillofacial Surgery School and Hospital of Stomatology, Peking UniversityAbstract 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.https://doi.org/10.1186/s13287-022-03033-5Pluripotent stem cellsThree-dimensional culturesSalivary glandsOrganogenesisModeling |
| spellingShingle | Siqi Zhang Yi Sui Shuang Yan Yifei Zhang Chong Ding Xiaodong Su Jingwei Xiong Shicheng Wei Retinoic acid and FGF10 promote the differentiation of pluripotent stem cells into salivary gland placodes Stem Cell Research & Therapy Pluripotent stem cells Three-dimensional cultures Salivary glands Organogenesis Modeling |
| 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 | Pluripotent stem cells Three-dimensional cultures Salivary glands Organogenesis Modeling |
| url | https://doi.org/10.1186/s13287-022-03033-5 |
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