TY  - BOOK
AU  - Kvedaraite,Egle
AU  - Milne,Paul
AU  - Khalilnezhad,Ahad
AU  - Chevrier,Marion
AU  - Sethi,Raman
AU  - Lee,Hong Kai
AU  - Hagey,Daniel W.
AU  - von Bahr Greenwood,Tatiana
AU  - Mouratidou,Natalia
AU  - Jädersten,Martin
AU  - Lee,Nicole Yee Shin
AU  - Minnerup,Lara
AU  - Yingrou,Tan
AU  - Dutertre,Charles-Antoine
AU  - Benac,Nathan
AU  - Hwang,You Yi
AU  - Lum,Josephine
AU  - Loh,Amos Hong Pheng
AU  - Jansson,Jessica
AU  - Teng,Karen Wei Weng
AU  - Khalilnezhad,Shabnam
AU  - Weili,Xu
AU  - Resteu,Anastasia
AU  - Liang,Tey Hong
AU  - Guan,Ng Lai
AU  - Larbi,Anis
AU  - Howland,Shanshan Wu
AU  - Arnell,Henrik
AU  - Andaloussi,Samir EL
AU  - Braier,Jorge
AU  - Rassidakis,Georgios
AU  - Galluzzo,Laura
AU  - Dzionek,Andrzej
AU  - Henter,Jan-Inge
AU  - Chen,Jinmiao
AU  - Collin,Matthew
AU  - Ginhoux,Florent
TI  - NOTCH dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
PY  - 2022///-12-23
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7614120; /pubmed/36525505
N2  - Langerhans 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
UR  - http://dx.doi.org/10.1126/sciimmunol.add3330
ER  -