000 03779 am a22006373u 4500
042 _adc
100 1 0 _aKvedaraite, Egle
_eauthor
_92596
700 1 0 _aMilne, Paul
_eauthor
_92597
700 1 0 _aKhalilnezhad, Ahad
_eauthor
_92598
700 1 0 _aChevrier, Marion
_eauthor
_92599
700 1 0 _aSethi, Raman
_eauthor
_92600
700 1 0 _aLee, Hong Kai
_eauthor
_92601
700 1 0 _aHagey, Daniel W.
_eauthor
_92602
700 1 0 _avon Bahr Greenwood, Tatiana
_eauthor
_92603
700 1 0 _aMouratidou, Natalia
_eauthor
_92604
700 1 0 _aJädersten, Martin
_eauthor
_92605
700 1 0 _aLee, Nicole Yee Shin
_eauthor
_92606
700 1 0 _aMinnerup, Lara
_eauthor
_92607
700 1 0 _aYingrou, Tan
_eauthor
_92608
700 1 0 _aDutertre, Charles-Antoine
_eauthor
_92609
700 1 0 _aBenac, Nathan
_eauthor
_92610
700 1 0 _aHwang, You Yi
_eauthor
_92611
700 1 0 _aLum, Josephine
_eauthor
_92612
700 1 0 _aLoh, Amos Hong Pheng
_eauthor
_92613
700 1 0 _aJansson, Jessica
_eauthor
_92614
700 1 0 _aTeng, Karen Wei Weng
_eauthor
_92615
700 1 0 _aKhalilnezhad, Shabnam
_eauthor
_92616
700 1 0 _aWeili, Xu
_eauthor
_92617
700 1 0 _aResteu, Anastasia
_eauthor
_92618
700 1 0 _aLiang, Tey Hong
_eauthor
_92619
700 1 0 _aGuan, Ng Lai
_eauthor
_92620
700 1 0 _aLarbi, Anis
_eauthor
_92621
700 1 0 _aHowland, Shanshan Wu
_eauthor
_92622
700 1 0 _aArnell, Henrik
_eauthor
_92623
700 1 0 _aAndaloussi, Samir EL
_eauthor
_92624
700 1 0 _aBraier, Jorge
_eauthor
_92625
700 1 0 _aRassidakis, Georgios
_eauthor
_92626
700 1 0 _aGalluzzo, Laura
_eauthor
_92627
700 1 0 _aDzionek, Andrzej
_eauthor
_92628
700 1 0 _aHenter, Jan-Inge
_eauthor
_92629
700 1 0 _aChen, Jinmiao
_eauthor
_92630
700 1 0 _aCollin, Matthew
_eauthor
_92631
700 1 0 _aGinhoux, Florent
_eauthor
_92632
245 0 0 _aNOTCH dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
260 _c2022-12-23.
500 _a/pmc/articles/PMC7614120/
500 _a/pubmed/36525505
520 _aLangerhans cell histiocytosis (LCH) is a potentially fatal neoplasm, characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase pathway activation. LCH cells may trigger destructive pathology yet remain in precarious state, finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well-known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity, and comparing LCH cells with normal MNPs within lesions. We found LCH-discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/Monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch dependent cooperativity between DC2 and DC3/monocyte lineages, during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring prior to fate commitment to DC2 and DC3/Monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
540 _a
540 _ahttps://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nSci Immunol
856 4 1 _uhttp://dx.doi.org/10.1126/sciimmunol.add3330
_zConnect to this object online.
999 _c2030
_d2030