Generation of live mice from haploid ESCs with germline-DMR deletions or switch
Abstract Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles i...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00757-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586031230091264 |
|---|---|
| author | Yongjian Ma Meng Yan Zhenfei Xie Hongling Zhang Zhoujie Li Yuanyuan Li Suming Yang Meiling Zhang Wen Li Jinsong Li |
| author_facet | Yongjian Ma Meng Yan Zhenfei Xie Hongling Zhang Zhoujie Li Yuanyuan Li Suming Yang Meiling Zhang Wen Li Jinsong Li |
| author_sort | Yongjian Ma |
| collection | DOAJ |
| description | Abstract Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles in development. However, what imprinting network is essential for development is still unclear. Here, we establish a stepwise system to reconstruct a development-related imprinting network, in which diploid embryonic stem cells (ESCs) are derived by fusing between parthenogenetic (PG)- and androgenetic (AG)-haploid embryonic stem cells (haESCs) with different DMR deletions (termed Ha-Ha-fusion system), followed by tetraploid complementation to produce all-haESC fetuses. Diploid ESCs fused between PG-haESCs carrying 8 maternally-derived DMR deletions and AG-haESCs with 2 paternally-derived DMR deletions give rise to live pups efficiently, among which, one lives to weaning. Strikingly, diploid ESCs derived from the fusion of PG-haESCs with 7 maternal DMR deletions and AG-haESCs with 2 paternal DMR deletions and maternal Snrpn-DMR deletion also support full-term embryonic development. Moreover, embryos reconstructed by injection of AG-haESCs with hypomethylated H19-DMR into oocytes with H19-DMR deletion develop into live mice sustaining inverted allelic gene expression. Together, our findings indicate that restoration of monoallelic expression of 10 imprinted regions is adequate for the full-term development of all-haESC pups, and it works irrespective of their parental origins. Meanwhile, Ha-Ha-fusion system provides a useful tool for deciphering imprinting regulation networks during embryonic development. |
| format | Article |
| id | doaj-art-0411d60952684d41a6928a03f41cedce |
| institution | Kabale University |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-0411d60952684d41a6928a03f41cedce2025-01-26T12:15:03ZengNature Publishing GroupCell Discovery2056-59682025-01-0111111410.1038/s41421-024-00757-xGeneration of live mice from haploid ESCs with germline-DMR deletions or switchYongjian Ma0Meng Yan1Zhenfei Xie2Hongling Zhang3Zhoujie Li4Yuanyuan Li5Suming Yang6Meiling Zhang7Wen Li8Jinsong Li9Key Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesAnimal Core Facility, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesCenter for Reproductive Medicine & Fertility Preservation Program, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong UniversityCenter for Reproductive Medicine & Fertility Preservation Program, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong UniversityKey Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of SciencesAbstract Genomic imprinting is required for sexual reproduction and embryonic development of mammals, in which, differentially methylated regions (DMRs) regulate the parent-specific monoallelic expression of imprinted genes. Numerous studies on imprinted genes have highlighted their critical roles in development. However, what imprinting network is essential for development is still unclear. Here, we establish a stepwise system to reconstruct a development-related imprinting network, in which diploid embryonic stem cells (ESCs) are derived by fusing between parthenogenetic (PG)- and androgenetic (AG)-haploid embryonic stem cells (haESCs) with different DMR deletions (termed Ha-Ha-fusion system), followed by tetraploid complementation to produce all-haESC fetuses. Diploid ESCs fused between PG-haESCs carrying 8 maternally-derived DMR deletions and AG-haESCs with 2 paternally-derived DMR deletions give rise to live pups efficiently, among which, one lives to weaning. Strikingly, diploid ESCs derived from the fusion of PG-haESCs with 7 maternal DMR deletions and AG-haESCs with 2 paternal DMR deletions and maternal Snrpn-DMR deletion also support full-term embryonic development. Moreover, embryos reconstructed by injection of AG-haESCs with hypomethylated H19-DMR into oocytes with H19-DMR deletion develop into live mice sustaining inverted allelic gene expression. Together, our findings indicate that restoration of monoallelic expression of 10 imprinted regions is adequate for the full-term development of all-haESC pups, and it works irrespective of their parental origins. Meanwhile, Ha-Ha-fusion system provides a useful tool for deciphering imprinting regulation networks during embryonic development.https://doi.org/10.1038/s41421-024-00757-x |
| spellingShingle | Yongjian Ma Meng Yan Zhenfei Xie Hongling Zhang Zhoujie Li Yuanyuan Li Suming Yang Meiling Zhang Wen Li Jinsong Li Generation of live mice from haploid ESCs with germline-DMR deletions or switch Cell Discovery |
| title | Generation of live mice from haploid ESCs with germline-DMR deletions or switch |
| title_full | Generation of live mice from haploid ESCs with germline-DMR deletions or switch |
| title_fullStr | Generation of live mice from haploid ESCs with germline-DMR deletions or switch |
| title_full_unstemmed | Generation of live mice from haploid ESCs with germline-DMR deletions or switch |
| title_short | Generation of live mice from haploid ESCs with germline-DMR deletions or switch |
| title_sort | generation of live mice from haploid escs with germline dmr deletions or switch |
| url | https://doi.org/10.1038/s41421-024-00757-x |
| work_keys_str_mv | AT yongjianma generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT mengyan generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT zhenfeixie generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT honglingzhang generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT zhoujieli generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT yuanyuanli generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT sumingyang generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT meilingzhang generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT wenli generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch AT jinsongli generationoflivemicefromhaploidescswithgermlinedmrdeletionsorswitch |