Developmental principles informing human pluripotent stem cell differentiation to cartilage and bone

Humphreys, Paul A.; Ferreira, M. Jamie; Woods, Steven Paul; Ogene, Leona; Kimber, Susan J.

doi:10.1016/j.semcdb.2021.11.024

Cited by 13 publications

(14 citation statements)

References 244 publications

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“…When we looked at the DEGs in pairwise comparisons between time points, we identified several genes with important roles in skeletal development. From day 0 to day 1 (transition from chondroprogenitors to chondroblasts) IHH , GDF5 , FGF8 , and WNT16 were amongst the top DEGs, which are all key components of chondrogenesis (13). We also noted a robust differential expression in transcripts involved in ECM production such as chondrolectin ( CHODL ), chondroitin sulfate N-acetylgalactosaminyltransferase 1 ( CSGALNACT1 ), MMP27 , COL14A1 , COL16A1 , matrilin-1 ( MATN1 ), and chondroadherin ( CHAD ), also in line with the literature (42).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The temporal transcriptomic signature of cartilage formation

Takács

Vágó

Póliska

et al. 2022

Preprint

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Chondrogenesis is a multistep process whereby cartilage progenitor cells generate a tissue with distinct structural and functional properties. Although several approaches to cartilage regeneration rely on the differentiation of implanted progenitor cells, the temporal transcriptomic landscape of in vitro chondrogenesis in different models has not been reported. Using RNA sequencing, we examined the differences between gene expression patterns during early cartilage formation in micromass cultures of embryonic limb bud-derived progenitors. Principal component analysis indicated a progressively different and distinct transcriptome during chondrogenesis. Differentially expressed genes (DEGs) based on pairwise comparisons of samples from consecutive days were classified into clusters and analysed. We confirmed the involvement of the top DEGs in chondrogenic differentiation with pathway analysis. We discovered several chondrogenesis-associated transcription factors and new collagen subtypes not previously linked to cartilage formation. These results provide, for the first time, a detailed insight into the molecular mechanism of in vitro chondrogenesis and provide a new gold standard for the temporal transcriptomic landscape of chondrogenic differentiation that may serve as a platform for new approaches in cartilage tissue engineering.

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Section: Discussionmentioning

confidence: 99%

“…This model is particularly useful for studying the early events of chondrogenesis. Several molecular pathways are involved in this complex process (13). However, the time course of transcriptomic events involved in the regulation of these pathways during in vitro chondrogenesis has not been fully explored.…”

Section: Introductionmentioning

confidence: 99%

The temporal transcriptomic signature of cartilage formation

Takács

Vágó

Póliska

et al. 2022

Preprint

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“…There are two bone formation pathways: (i) intramembranous ossification in which bone rises directly within preexisting mesenchymal connective tissue, and (ii) endochondral ossification in which bone rises within hyaline cartilage, developed from mesenchyme). After birth, MSCs and skeleton stem cells (SSCs) are responsible for bone homeostasis in the body [ 16 , 17 , 18 ].…”

Section: Stem Cellsmentioning

confidence: 99%

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders

Mishra

Kumar

Mishra

et al. 2023

Cells

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Stem cells’ self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells’ self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

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“…This model is particularly useful for studying early events of chondrogenesis. Several molecular pathways regulate in this complex process ( 14 ). However, the time course of transcriptomic events involved in the regulation of these pathways during in vitro chondrogenesis has not been fully explored.…”

Section: Introductionmentioning

confidence: 99%

The temporal transcriptomic signature of cartilage formation

Takács

Vágó

Póliska

et al. 2023

Nucleic Acids Research

View full text Add to dashboard Cite

Chondrogenesis is a multistep process, in which cartilage progenitor cells generate a tissue with distinct structural and functional properties. Although several approaches to cartilage regeneration rely on the differentiation of implanted progenitor cells, the temporal transcriptomic landscape of in vitro chondrogenesis in different models has not been reported. Using RNA sequencing, we examined differences in gene expression patterns during cartilage formation in micromass cultures of embryonic limb bud-derived progenitors. Principal component and trajectory analyses revealed a progressively different and distinct transcriptome during chondrogenesis. Differentially expressed genes (DEGs), based on pairwise comparisons of samples from consecutive days were classified into clusters and analysed. We confirmed the involvement of the top DEGs in chondrogenic differentiation using pathway analysis and identified several chondrogenesis-associated transcription factors and collagen subtypes that were not previously linked to cartilage formation. Transient gene silencing of ATOH8 or EBF1 on day 0 attenuated chondrogenesis by deregulating the expression of key osteochondrogenic marker genes in micromass cultures. These results provide detailed insight into the molecular mechanism of chondrogenesis in primary micromass cultures and present a comprehensive dataset of the temporal transcriptomic landscape of chondrogenesis, which may serve as a platform for new molecular approaches in cartilage tissue engineering.

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Developmental principles informing human pluripotent stem cell differentiation to cartilage and bone

Cited by 13 publications

References 244 publications

The temporal transcriptomic signature of cartilage formation

The temporal transcriptomic signature of cartilage formation

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders

The temporal transcriptomic signature of cartilage formation

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