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Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

ABSTRACT: Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

PROVIDER: PRJNA413810 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6155050_1.fastq.gz	Fastqsanger.gz
	SRR6155050_2.fastq.gz	Fastqsanger.gz
	SRR6155060_1.fastq.gz	Fastqsanger.gz
	SRR6155060_2.fastq.gz	Fastqsanger.gz
	SRR6155070_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA-seq analysis reveals the progression of human osteoarthritis

Project description:Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index analysis and correspondence analysis. We identified seven molecularly defined populations of chondrocytes in human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles and transcriptional networks among chondrocytes at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA.

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Single-cell RNA-seq analysis reveals the progression of human osteoarthritis.

Project description:ObjectivesUnderstanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq).MethodsWe performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis.ResultsWe identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA.ConclusionsOur results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.

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Sirt6 attenuates chondrocyte senescence and osteoarthritis progression

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Project description:Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is helpful for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using highly sensitive single-cell RNA sequencing technology, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture.

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