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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Na\u00efve human pluripotent stem cells (hPSCs) represent an in vitro analog of the pre-implantation epiblast \u2013 the founder tissue of the embryo proper. A widely held assumption, based on prior studies in the mouse system, was that na\u00efve hPSCs are restricted in their differentiation potential toward more mature stages of epiblast development, as a prelude to gastrulation. However, over the past 5 years, a growing body of literature has demonstrated that na\u00efve hPSCs have an expanded lineage potential toward a broad range of embryonic and extraembryonic fates and can even be used as a starting point for generating 8-cell-like cells. The most emphatic demonstration of the broad lineage potential of na\u00efve hPSCs is their remarkable capacity to self-organize into blastocyst-like structures (\u201cblastoids\u201d) that model all three lineages of the pre-implantation embryo and can be cultured to post-implantation stages. Here, we discuss the broad spectrum of cell fates accessible from na\u00efve hPSCs and the signaling pathways that guide the exit from the ground state of human pluripotency.<\/jats:p>","DOI":"10.1007\/s00018-025-05984-3","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:20:26Z","timestamp":1767702026000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exiting the ground state: the broad spectrum of cell fates accessible from na\u00efve human pluripotent stem cells"],"prefix":"10.1007","volume":"83","author":[{"given":"Kyoung-mi","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6943-7858","authenticated-orcid":false,"given":"Thorold W.","family":"Theunissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"issue":"7618","key":"5984_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature19096","volume":"537","author":"T Nakamura","year":"2016","unstructured":"Nakamura T et al (2016) A developmental coordinate of pluripotency among mice, monkeys and humans. 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