ArticleJournal of cellular physiology2020
Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell-transcriptomics.
Article in Journal of cellular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- The notochord: development, disease and stem cell-based modelling.Development (Cambridge, England) · 2026Review
- Chondrogenic potential of mesenchymal progenitors from somatic and cartilage-derived iPSCs is predicted by their transcriptomic signatures.Genes & diseases · 2026Article
- Mesenchymal stem cell and exosome-based therapies for degenerative disc disease: from mechanisms to clinical translation.Frontiers in cell and developmental biology · 2026Review
- Reversion of passaged nucleus pulposus cells to notochordal-type cells by FoxA2 upregulation.NPJ Regenerative medicine · 2025Article
- Insights into chondrocyte populations in cartilaginous tissues at the single-cell level.Nature reviews. Rheumatology · 2025Review
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- In vitro modelling of anterior primitive streak patterning with human pluripotent stem cells identifies the path to notochord progenitors.Development (Cambridge, England) · 2024Article
- Enhanced osteogenic potential of iPSC-derived mesenchymal progenitor cells following genome editing of GWAS variants in the RUNX1 gene.Bone research · 2024Article
- Single-cell Transcriptomic Studies Unveil Potential Nodes of the Notochord Gene Regulatory Network.Integrative and comparative biology · 2024Review
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- Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization.JOR spine · 2023Article
- Intervertebral Disc Progenitors: Lessons Learned from Single-Cell RNA Sequencing and the Role in Intervertebral Disc Regeneration.Bioengineering (Basel, Switzerland) · 2023Article
- Human Embryonic Stem-Cell-Derived Exosomes Repress NLRP3 Inflammasome to Alleviate Pyroptosis in Nucleus Pulposus Cells by Transmitting miR-302c.International journal of molecular sciences · 2023Article
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- pH-sensing G protein-coupled orphan receptorPeerJ · 2023Article
- Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration.International journal of molecular sciences · 2022Review
- Review
- Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Intervertebral disc degeneration (IDD) is a public health dilemma as it is associated with low back and neck pain, a frequent reason for patients to visit the physician. During IDD, nucleus pulposus (NP), the central compartment of intervertebral disc (IVD) undergo degeneration. Stem cells have been adopted as a promising biological source to regenerate the IVD and restore its function. Here, we describe a simple, two-step differentiation strategy using a cocktail of four factors (LDN, AGN, FGF, and CHIR) for efficient derivation of notochordal cells from human embryonic stem cells (hESCs). We employed a CRISPR/Cas9 based genome-editing approach to knock-in the mCherry reporter vector upstream of the 3' untranslated region of the Noto gene in H9-hESCs and monitored notochordal cell differentiation. Our data show that treatment of H9-hESCs with the above-mentioned four factors for 6 days successfully resulted in notochordal cells. These cells were characterized by morphology, immunostaining, and gene and protein expression analyses for established notochordal cell markers including FoxA2, SHH, and Brachyury. Additionally, pan-genomic high-throughput single cell RNA-sequencing revealed an efficient and robust notochordal differentiation. We further identified a key regulatory network consisting of eight candidate genes encoding transcription factors including PAX6, GDF3, FOXD3, TDGF1, and SOX5, which are considered as potential drivers of notochordal differentiation. This is the first single cell transcriptomic analysis of notochordal cells derived from hESCs. The ability to efficiently obtain notochordal cells from pluripotent stem cells provides an additional tool to develop new cell-based therapies for the treatment of IDD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.