JOM KITA KE POLITEKNIK

NOTCH dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology (Record no. 2194)

MARC details
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Personal name Kvedaraite, Egle
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9 (RLIN) 2596
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Title NOTCH dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Date of publication, distribution, etc. 2022-12-23.
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General note /pmc/articles/PMC7614120/
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General note /pubmed/36525505
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Summary, etc. 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.
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Terms governing use and reproduction
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Terms governing use and reproduction https://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.
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Language note en
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Genre/form data or focus term Text
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Personal name Milne, Paul
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9 (RLIN) 2597
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Personal name Khalilnezhad, Ahad
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9 (RLIN) 2598
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Personal name Chevrier, Marion
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9 (RLIN) 2599
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Personal name Sethi, Raman
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Personal name Lee, Hong Kai
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Personal name Hagey, Daniel W.
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Personal name von Bahr Greenwood, Tatiana
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Personal name Mouratidou, Natalia
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Personal name Jädersten, Martin
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9 (RLIN) 2605
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Personal name Lee, Nicole Yee Shin
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9 (RLIN) 2606
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Personal name Minnerup, Lara
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Personal name Yingrou, Tan
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Personal name Dutertre, Charles-Antoine
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Personal name Benac, Nathan
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Personal name Hwang, You Yi
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Personal name Lum, Josephine
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Personal name Loh, Amos Hong Pheng
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Personal name Jansson, Jessica
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Personal name Teng, Karen Wei Weng
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Personal name Khalilnezhad, Shabnam
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Personal name Weili, Xu
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Personal name Resteu, Anastasia
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Personal name Liang, Tey Hong
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Personal name Guan, Ng Lai
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Personal name Larbi, Anis
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Personal name Howland, Shanshan Wu
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9 (RLIN) 2622
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Personal name Arnell, Henrik
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Personal name Andaloussi, Samir EL
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Personal name Braier, Jorge
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9 (RLIN) 2625
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Personal name Rassidakis, Georgios
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Personal name Galluzzo, Laura
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Personal name Dzionek, Andrzej
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Personal name Henter, Jan-Inge
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9 (RLIN) 2629
700 10 - ADDED ENTRY--PERSONAL NAME
Personal name Chen, Jinmiao
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9 (RLIN) 2630
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Personal name Collin, Matthew
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9 (RLIN) 2631
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Personal name Ginhoux, Florent
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9 (RLIN) 2632
786 0# - DATA SOURCE ENTRY
Note Sci Immunol
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1126/sciimmunol.add3330">http://dx.doi.org/10.1126/sciimmunol.add3330</a>
Public note Connect to this object online.

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