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Single-cell RNA-seq of airspace cellular subsets after inflammation and membrane damage

ABSTRACT: Single-cell RNA-seq of airspace cellular subsets after inflammation and membrane damage

PROVIDER: PRJNA729770 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14525708_1.fastq.gz	Fastqsanger.gz
	SRR14525708_2.fastq.gz	Fastqsanger.gz
	SRR14525709_1.fastq.gz	Fastqsanger.gz
	SRR14525709_2.fastq.gz	Fastqsanger.gz
	SRR14525710.fastq.gz	Fastqsanger.gz

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Project description:The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune mediated inflammatory diseases (IMIDs). Yet, despite their key role in disease, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue driven pathologies observed in IMIDs such as inflammation and damage . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of FAPa+ synovial cells suppressed both inflammation and bone erosions in murine models of resolving and persistent arthritis. Single cell transcriptional analysis identified two distinct fibroblast subsets: FAPa+ THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPa+ THY1- destructive fibroblasts restricted to the synovial lining. When adoptively transferred into the joint, FAPa+ THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation whereas transfer of FAPa+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell based therapies aimed at modulating inflammation and tissue damage.

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