{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:01:58Z","timestamp":1784656918003,"version":"3.55.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HD102639"],"award-info":[{"award-number":["R01-HD102639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Abnormal decidual natural killer cell (dNK) function is linked to pregnancy complications occurring in both early and late gestation, including recurrent pregnancy loss, preeclampsia, and preterm birth. Exploration of dNK heterogeneity as it relates to function is an active area of research; however, most of this work has focused on early gestation. Using flow cytometric and transcriptomic single-cell definitions of dNK subtypes, we characterized dNK heterogeneity in term dNK within both chorioamniotic membranes and the basal plate. We also applied aptamer-based secretome profiling to first trimester and term dNK and found dNK-specific proteins\u2014VEGF and PLGF\u2014to be reduced at term. We further determined that, compared to first trimester dNK, term dNK have reduced cytotoxicity against target cells. Finally, we applied this knowledge to establish a protocol for differentiation of induced pluripotent stem cells (iPSC) into functional dNK. We found that treatment with TGF\u03b2 enriched for dNK2 subtype, while inducing dNK markers, CD9 and CD103. We evaluated function using cytokine and degranulation assays, aptamer-based secretome profiling, and cytotoxicity assays. We found that iPSC-dNK are functionally most similar to primary dNK. Further, TGF\u03b2 iPSC-dNK had reduced GM-CSF in response to PMA\/I and increased secretion of VEGF and other first trimester-specific proteins\u2013supportive of a shift towards an early gestation, dNK2-dominant, phenotype. We conclude that changes in dNK function across gestation reflect shifts in dNK subtypes that can be reproducibly derived from iPSC, providing a new method for modeling dNK and laying the foundation for cell-based therapeutics for reproductive disease.<\/jats:p>","DOI":"10.1093\/stmcls\/sxag020","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:37:57Z","timestamp":1776339477000},"source":"Crossref","is-referenced-by-count":0,"title":["Derivation of functional early gestation decidual natural killer cell subtypes from induced pluripotent stem cells"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-823X","authenticated-orcid":false,"given":"Virginia Chu","family":"Cheung","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, University of California San Diego , La Jolla, CA 92093,","place":["United States"]},{"name":"Sanford Consortium for Regenerative Medicine, University 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92093,","place":["United States"]},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of California San Diego , La Jolla, CA 92093,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E","family":"Morey","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of California San Diego , La Jolla, CA 92093,","place":["United States"]},{"name":"Sanford Consortium for Regenerative Medicine, University of California San Diego , La Jolla, CA 92093,","place":["United States"]},{"name":"Center for Perinatal Discovery, University of California San Diego , La Jolla, CA 92093,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisjesus S","family":"Cruz","sequence":"additional","affiliation":[{"name":"Sanford Consortium for Regenerative Medicine, University of California San Diego , La Jolla, CA 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