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Although various features of EPSCs have been defined, their ability to directly transfer extended pluripotency to differentiated somatic cells by cell fusion remains to be elucidated. Here, we derived EPSCs from eight-cell mouse embryos and confirmed their extended pluripotency at the molecular level and extraembryonic differentiation ability. Then, they were fused with OG2+\/\u2212 ROSA+\/\u2212 neural stem cells (NSCs) by the polyethylene-glycol (PEG)-mediated method and further analyzed. The resulting fused hybrid cells exhibited pluripotential markers with upregulated EPSC-specific gene expression. Furthermore, the hybrid cells contributed to the extraembryonic and embryonic lineages in vivo and in vitro. RNA sequencing analysis confirmed that the hybrid cells showed distinct global expression patterns resembling EPSCs without parental expression of NSC markers, indicating the complete acquisition of extended pluripotency and the erasure of the somatic memory of NSCs. Furthermore, ultrastructural observation and metabolic analysis confirmed that the hybrid cells rearranged the mitochondrial morphology and bivalent metabolic profile to those of EPSCs. In conclusion, the extended pluripotency of EPSCs could be transferred to somatic cells through fusion-induced reprogramming.<\/jats:p>","DOI":"10.3390\/cells11203266","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T21:11:51Z","timestamp":1666041111000},"page":"3266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Developmental Potency and Metabolic Traits of Extended Pluripotency Are Faithfully Transferred to Somatic Cells via Cell Fusion-Induced Reprogramming"],"prefix":"10.3390","volume":"11","author":[{"given":"Jae-Hoon","family":"Song","sequence":"first","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"},{"name":"3D Tissue Culture Research Center, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7677-5978","authenticated-orcid":false,"given":"Joonhyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yean-Ju","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonwoo","family":"La","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5237-2266","authenticated-orcid":false,"given":"Tae-Kyung","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"},{"name":"3D Tissue Culture Research Center, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwonho","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1441","authenticated-orcid":false,"given":"Jeong-Tae","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, Seoul 05029, Korea"},{"name":"3D Tissue Culture Research Center, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.stem.2017.12.011","article-title":"Capturing Totipotent Stem Cells","volume":"22","author":"Baker","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11167","DOI":"10.1038\/s41598-021-90653-1","article-title":"Totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage","volume":"11","author":"Maemura","year":"2021","journal-title":"Sci. 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