Transcriptomic landscape of circulating mononuclear phagocytes in Langerhans cell histiocytosis at the single-cell level.

Autor:	Shi H; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., He H; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Cui L; Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.; Beijing Key Laboratory of Pediatric Hematology Oncology-National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Kvedaraite E; Childhood Cancer Research Unit, Department of Women's and Children's Health, and.; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden., Bian Z; Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China., Huang T; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Lee CZW; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), BIOPOLIS, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Li Z; Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., He J; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Gong Y; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China., Li Z; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China., Zhou J; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China., Zeng Y; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China., Li X; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Ni Y; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China., Bai Z; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Liu C; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China., Li N; Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Ma H; Beijing Key Laboratory of Pediatric Hematology Oncology-National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Wang D; Beijing Key Laboratory of Pediatric Hematology Oncology-National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Lan Y; Laboratory for Regenerative Medicine, Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China., Ginhoux F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), BIOPOLIS, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.; Shanghai Institute of Immunology, Shanghai School of Medicine, Shanghai, China; and.; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Zhang R; Beijing Key Laboratory of Pediatric Hematology Oncology-National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Liu B; State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China.; State Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Oct 07; Vol. 138 (14), pp. 1237-1248.
DOI:	10.1182/blood.2020009064
Abstrakt:	Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm caused by aberrant activation of the mitogen-activated protein kinase (MAPK) pathway. Circulating myeloid cells from patients often carry disease-associated mutations and can be differentiated into langerinhigh LCH-like cells in vitro, but their detailed immune-phenotypic and molecular profiles are lacking and could shed key insights into disease biology. Here we recruited 217 pediatric LCH patients and took blood and tissue samples for BRAFV600E analysis. Immune-phenotyping of the circulating Lin-HLA-DR+ immune population in 49 of these patients revealed that decreased frequency of plasmacytoid dendritic cells was significantly linked to disease severity. By single-cell RNA sequencing of samples from 14 patients, we identified key changes in expression of RAS-MAPK-extracellular signal-regulated kinase (ERK) signaling-related genes and transcription factors in distinct members of the mononuclear phagocyte system in the presence of BRAFV600E. Moreover, treatment of patients with the BRAF inhibitor dabrafenib resulted in MAPK cascade inhibition, inflammation prevention, and regulation of cellular metabolism within mononuclear phagocytes. Finally, we also observed elevated expression of RAS-MAPK-ERK signaling-related genes in a CD207+CD1a+ cell subcluster in skin. Taken together, our data extend the molecular understanding of LCH biology at single-cell resolution, which might contribute to improvement of clinical diagnostics and therapeutics, and aid in the development of personalized medicine approaches. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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