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Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

ABSTRACT: Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

PROVIDER: PRJNA420979 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6343635_1.fastq.gz	Fastqsanger.gz
	SRR6343635_2.fastq.gz	Fastqsanger.gz
	SRR6343636_1.fastq.gz	Fastqsanger.gz
	SRR6343636_2.fastq.gz	Fastqsanger.gz
	SRR6343637_1.fastq.gz	Fastqsanger.gz

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Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

Project description:In this study we explore the gene set that is selectively expressed in chondrocytes and therefore determines the unique properties and functions of cartilage tissue. Through identification of cartilage-selective transcription factors, lncRNAs, enhancers and protein-coding genes, we address the determinants of cartilage-selective gene expression, including interactions among the regulatory molecules and selectively active promoters, which define the pattern of gene expression and ultimately chondrocyte biology. Among 34 previously undescribed cartilage selective lncRNAs, one particular lncRNA was found to be co-expressed with and reciprocally regulated by SOX9, the master transcriptional regulator of chondrogenesis, revealing a new aspect of the regulation of the gene for this critical determinant of chondrocyte function. Finally, we relate cartilage-selective gene expression to the human and mouse skeletal disorders that result from mutations in many of the selectively regulated genes, providing clinical context to the basic biological discoveries.

2017-12-08 | GSE107649 | GEO

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.

Project description:BACKGROUND:Chondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved. RESULTS:In this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes. CONCLUSIONS:Our findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.

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Gene expression profile at single vell level of growth plate chondrocytes [scRNA-seq]

Project description:Gowth plate chondrocytes include heterogenous cell population and cellular diversity of these chondrocytes remains to be elucidated. We used single cell RNA sequencing to uncover the diverssity of growth plate chondrocytes and identify noel marker genes selectively expressed in pre-hypertrophic chondrocytes.

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Project description:Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. 6 pairs of HZ vs RZ were compared by microarray. Experiment Overall Design: Growth plate chondrocytes were isolated from the distal metacarpus of young dairy cattle (all under 10 mo of age), the chondrocytes were released from the extracellular matrix by digestion with Collagenase P for 4 hours, and the various zones of the growth plate were separated by density centrifugation. The least-dense Hypertrophic Zone (HZ) cells were compared to the most-dense Reserve Zone (RZ) cells. Six independent sample pairs of HZ vs RZ were compared by microarray.

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Project description:We revealed the unique molecular signature of slow-cycling chondrocytes of the postnatal growth plate.

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