WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism
Abstract Mammalian pre‐implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited acce...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412222 |
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| author | Shiyu An Shuyue Hou Feifei Xu Huanyu Yan Wenyi Zhang Jinfeng Xiang Haoran Chen Hanwen Zhang Lingling Dong Xiaobin Sun Ran Huo Yun Chen Xi Wang Yang Yang |
| author_facet | Shiyu An Shuyue Hou Feifei Xu Huanyu Yan Wenyi Zhang Jinfeng Xiang Haoran Chen Hanwen Zhang Lingling Dong Xiaobin Sun Ran Huo Yun Chen Xi Wang Yang Yang |
| author_sort | Shiyu An |
| collection | DOAJ |
| description | Abstract Mammalian pre‐implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell‐derived blastocyst‐like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions. |
| format | Article |
| id | doaj-art-0d10301d7b1248c290255fb7cf78b962 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0d10301d7b1248c290255fb7cf78b9622025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202412222WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic MetabolismShiyu An0Shuyue Hou1Feifei Xu2Huanyu Yan3Wenyi Zhang4Jinfeng Xiang5Haoran Chen6Hanwen Zhang7Lingling Dong8Xiaobin Sun9Ran Huo10Yun Chen11Xi Wang12Yang Yang13State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaSchool of Pharmacy Nanjing Medical University Nanjing 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaFourth Clinical Medicine College Nanjing Medical University Nanjing 210004 ChinaSchool of Pharmacy Nanjing Medical University Nanjing 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaState Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing Jiangsu 211166 ChinaAbstract Mammalian pre‐implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell‐derived blastocyst‐like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.https://doi.org/10.1002/advs.202412222glycolysishuman embryonic developmentLDHAtrophectoderm lineage commitmentWDR36 |
| spellingShingle | Shiyu An Shuyue Hou Feifei Xu Huanyu Yan Wenyi Zhang Jinfeng Xiang Haoran Chen Hanwen Zhang Lingling Dong Xiaobin Sun Ran Huo Yun Chen Xi Wang Yang Yang WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism Advanced Science glycolysis human embryonic development LDHA trophectoderm lineage commitment WDR36 |
| title | WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism |
| title_full | WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism |
| title_fullStr | WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism |
| title_full_unstemmed | WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism |
| title_short | WDR36 Regulates Trophectoderm Differentiation During Human Preimplantation Embryonic Development Through Glycolytic Metabolism |
| title_sort | wdr36 regulates trophectoderm differentiation during human preimplantation embryonic development through glycolytic metabolism |
| topic | glycolysis human embryonic development LDHA trophectoderm lineage commitment WDR36 |
| url | https://doi.org/10.1002/advs.202412222 |
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