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How tissue-resident uterine NK cells arise from blood-based precursor cells is unknown. Here, we identify early tissue immigrants, developmental intermediates, and mature effector states in human endometrium. We also uncover a transcriptional program of TGF-\u03b2 responsive genes that is upregulated in recent tissue immigrants prior to expression of effector molecules. Differences in TGF-\u03b2 responsiveness of uNK precursors promote differential expression of divergent effector uNK subsets, resulting in either repression or preservation of cytotoxic effector potential. Collectively, these data suggest a molecular mechanism of tissue-resident uNK maturation that links tissue residency with the acquisition of divergent effector functions in human endometrium.<\/jats:p>","DOI":"10.1101\/2025.07.05.663267","type":"posted-content","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T04:30:14Z","timestamp":1752121814000},"source":"Crossref","is-referenced-by-count":1,"title":["A developmental program of early residency promotes the differentiation of divergent uterine NK cell subsets in humans"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-8128","authenticated-orcid":false,"given":"Morgan","family":"Greene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Asiimwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markayla","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Epstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittney","family":"Knott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Clevenger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly E.","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aharon G.","family":"Freud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn C.","family":"Little","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige M.","family":"Porrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025071114402251000_2025.07.05.663267v1.1","doi-asserted-by":"crossref","unstructured":"Craven, C.M. , Morgan, T. , and Warda, K. 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