Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests
Abstract Background The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating...
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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/s13287-022-03019-3 |
| _version_ | 1818017912955338752 |
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| author | Sheng Yang Zhen Liu Shengda Wu Lang Zou Yanpei Cao Hongjia Xu Jingfeng Huang Qingyan Tian Fanggui Wu Panpan Li Shuping Peng Cijun Shuai |
| author_facet | Sheng Yang Zhen Liu Shengda Wu Lang Zou Yanpei Cao Hongjia Xu Jingfeng Huang Qingyan Tian Fanggui Wu Panpan Li Shuping Peng Cijun Shuai |
| author_sort | Sheng Yang |
| collection | DOAJ |
| description | Abstract Background The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs. Methods iPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development. Results First, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes. Conclusions Human PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo. |
| first_indexed | 2024-04-14T07:33:00Z |
| format | Article |
| id | doaj.art-74be6b1e1e494d77acf4423f90042fb7 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-14T07:33:00Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-74be6b1e1e494d77acf4423f90042fb72022-12-22T02:05:48ZengBMCStem Cell Research & Therapy1757-65122022-07-0113111110.1186/s13287-022-03019-3Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nestsSheng Yang0Zhen Liu1Shengda Wu2Lang Zou3Yanpei Cao4Hongjia Xu5Jingfeng Huang6Qingyan Tian7Fanggui Wu8Panpan Li9Shuping Peng10Cijun Shuai11The Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityThe Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityDepartment of Obstetrics and Gynecology, Shenzhen University General HospitalThe Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityDepartment of Obstetrics and Gynecology, Shenzhen University General HospitalDepartment of Obstetrics and Gynecology, Shenzhen University General HospitalDepartment of Obstetrics and Gynecology, Shenzhen University General HospitalThe Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityThe Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityThe Reproduction Medical Center, The Third Affiliated Hospital of Shenzhen UniversityNHC Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South UniversityInstitute of Additive Manufacturing, Jiangxi University of Science and TechnologyAbstract Background The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs. Methods iPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development. Results First, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes. Conclusions Human PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo.https://doi.org/10.1186/s13287-022-03019-3Primordial germ cellsInduced pluripotent stem cellsMeiosisDifferentiationOocyteWnt signaling pathway |
| spellingShingle | Sheng Yang Zhen Liu Shengda Wu Lang Zou Yanpei Cao Hongjia Xu Jingfeng Huang Qingyan Tian Fanggui Wu Panpan Li Shuping Peng Cijun Shuai Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests Stem Cell Research & Therapy Primordial germ cells Induced pluripotent stem cells Meiosis Differentiation Oocyte Wnt signaling pathway |
| title | Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| title_full | Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| title_fullStr | Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| title_full_unstemmed | Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| title_short | Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| title_sort | meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian nests |
| topic | Primordial germ cells Induced pluripotent stem cells Meiosis Differentiation Oocyte Wnt signaling pathway |
| url | https://doi.org/10.1186/s13287-022-03019-3 |
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