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000280288 1001_ $$00009-0002-2540-5736$$aReiß, Julian$$b0
000280288 245__ $$aA human NK cell progenitor that originates in the thymus and generates KIR+NKG2A- NK cells.
000280288 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2025
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000280288 520__ $$aKIR+NKG2A- natural killer (NK) cells have the unique ability to detect down-regulation of single HLA-I allotypes, frequently occurring in malignantly transformed and virus-infected cells. We have recently shown that circulating innate lymphoid cells 1 (cILC1s) have the potential to generate such KIR+NKG2A- NK cells, but their developmental origin was unknown. Here, we demonstrate that the development of cILC1 is thymus dependent and identify a putative progenitor of cILC1s in the thymus (thyILC1). Single-cell RNA sequencing analysis revealed a close relationship of thyILC1s to CD34+ double-negative thymocytes. Both generated comparable NK cell frequencies, while only thyILC1s could be efficiently differentiated into KIR+NKG2A- NK cells. Last, patients with FOXN1 haploinsufficiency, showing congenital thymic hypoplasia, exhibited a profound deficiency of cILC1s but not cILC2s and cILC3s, demonstrating their specific thymus dependency. Together, the data suggest that thyILC1s are the source of a thymus-dependent NK cell differentiation pathway that promotes generation of KIR+NKG2A- NK cells.
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000280288 650_7 $$2NLM Chemicals$$aNK Cell Lectin-Like Receptor Subfamily C
000280288 650_7 $$2NLM Chemicals$$aReceptors, KIR
000280288 650_7 $$2NLM Chemicals$$aKLRC1 protein, human
000280288 650_2 $$2MeSH$$aHumans
000280288 650_2 $$2MeSH$$aKiller Cells, Natural: metabolism
000280288 650_2 $$2MeSH$$aKiller Cells, Natural: cytology
000280288 650_2 $$2MeSH$$aKiller Cells, Natural: immunology
000280288 650_2 $$2MeSH$$aThymus Gland: cytology
000280288 650_2 $$2MeSH$$aThymus Gland: immunology
000280288 650_2 $$2MeSH$$aThymus Gland: metabolism
000280288 650_2 $$2MeSH$$aNK Cell Lectin-Like Receptor Subfamily C: metabolism
000280288 650_2 $$2MeSH$$aCell Differentiation
000280288 650_2 $$2MeSH$$aReceptors, KIR: metabolism
000280288 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000280288 7001_ $$00000-0001-5647-4262$$aGhosh, Sujal$$b1
000280288 7001_ $$aScheid, Michael$$b2
000280288 7001_ $$aGraafen, Lea$$b3
000280288 7001_ $$00009-0001-0361-6375$$aScherenschlich, Nadine$$b4
000280288 7001_ $$00000-0002-0725-4199$$aWeinhold, Sandra$$b5
000280288 7001_ $$00000-0001-8818-4219$$aRaba, Katharina$$b6
000280288 7001_ $$0P:(DE-2719)9002116$$aPaulusch, Stefan$$b7$$udzne
000280288 7001_ $$0P:(DE-2719)9000846$$aDe Dominico, Elena$$b8
000280288 7001_ $$aPham, Thi X U$$b9
000280288 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc$$b10
000280288 7001_ $$aLaws, Hans-Jürgen$$b11
000280288 7001_ $$00000-0002-9945-8833$$aNiehues, Tim$$b12
000280288 7001_ $$aBorkhardt, Arndt$$b13
000280288 7001_ $$00000-0001-9553-1987$$aUhrberg, Markus$$b14
000280288 7001_ $$00000-0003-0477-2748$$aBennstein, Sabrina B$$b15
000280288 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.adv9650$$gVol. 11, no. 32, p. eadv9650$$n32$$peadv9650$$tScience advances$$v11$$x2375-2548$$y2025
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