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Tenogenic induction from induced pluripotent stem cells unveils the trajectory towards tenocyte differentiation.

ABSTRACT: Tenogenic induction from induced pluripotent stem cells unveils the trajectory towards tenocyte differentiation.

PROVIDER: PRJNA707440 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13884949_1.fastq.gz	Fastqsanger.gz
	SRR13884949_2.fastq.gz	Fastqsanger.gz
	SRR13884950_1.fastq.gz	Fastqsanger.gz
	SRR13884950_2.fastq.gz	Fastqsanger.gz
	SRR13884951_1.fastq.gz	Fastqsanger.gz

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Tenogenic induction from induced pluripotent stem cells unveils the trajectory towards tenocyte differentiation.

Project description:The musculoskeletal system is integrated by tendons that are characterized by expression of a functionally important transcription factor Scleraxis (Scx). To date, there has been no solid culture system for tenogenic differentiation. Here we developed the tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence that reflects a series of dynamic differentiation process. Among several developmentally relevant factors, TGF-2 was the most potent inducer for differentiation of tenocytes expressing Tenomodulin, a mature differentiation marker. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters including mature tenocyte population and tenogenic differentiation trajectory, which well recapitulates in vivo developmental process. Dataset of scRNA-seq and transcriptome of Scx deficient tendon enabled identification of Scx-related genes in which tendon-related genes are enriched. Collectively, this study leads to a new opportunity for tendon research and provides further insight into mechanistic understanding of the differentiation pathway to a tenogenic fate.

2022-03-09 | GSE168451 | GEO

Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation.

Project description:The musculoskeletal system is integrated by tendons that are characterized by the expression of scleraxis (Scx), a functionally important transcription factor. Here, we newly developed a tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence, which reflects a dynamic differentiation process. Among several developmentally relevant factors, transforming growth factor-beta 2 (TGF-β2) was the most potent inducer for differentiation of tenomodulin-expressing mature tenocytes. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters, including mature tenocyte population and tenogenic differentiation trajectory, which recapitulated the in vivo developmental process. Analysis of the scRNA-seq dataset highlighted the importance of retinoic acid (RA) as a regulatory pathway of tenogenic differentiation. RA signaling was shown to have inhibitory effects on entheseal chondrogenic differentiation as well as TGF-β2-dependent tenogenic/fibrochondrogenic differentiation. The collective findings provide a new opportunity for tendon research and further insight into the mechanistic understanding of the differentiation pathway to a tenogenic fate.

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Collagen I and fibromodulin induce tenogenic differentiation of hASCs

Project description:Collagen I and fibromodulin, which was immobilized on PLCL nanoyarn, induced tenogenic differentiation of hASCs

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Project description:GDF5 is a potent tenogenic differentiation inducer. We previously demonstrated that GDF5 induced in vitro tenogenesis of human bone marrow-derived stromal cells (hMSC). We used microarrays to detail the global gene expression profiles underlying tenogenesis and identified distinct classes of up-regulated genes during this process.

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Project description:The extremity tendons and bones are derived from limb bud mesenchyme, which eventually become cells of different tissues. Despite their common origin, it was widely believed that tenocytes and skeletal cells are distinct lineages without interconversion. However, we found that periosteal skeletal progenitor cells could transform between osteogenic and tenogenic commitment. SCX can label the periosteal progenitor cell population. Loss of Piezo1 arrests the periosteal progenitor cells in a progenitor state. Piezo1 deficiency leads to upregulation of Scx expression due to the inhibited YAP nuclear localization. Loss of Piezo1 showed increased tenogenic marker genes and decreased osteogenic marker genes. The periosteal progenitor cells can regenerate the injured tendon more robustly when Piezo1 is absent. Taken together, our data reveal that periosteal SCX+ progenitor cells compromise the osteogenic ability and acquire the tenocyte-biased lineage commitment after loss of Piezo1, providing a strategy to modulate the periosteal progenitor cells for tissue regeneration.

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