ArticleStem cell research & therapy2020
Genetic barcoding reveals clonal dominance in iPSC-derived mesenchymal stromal cells.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- A multi-kingdom genetic barcoding system for precise clone isolation.Nature biotechnology · 2026Article
- Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cell Barcoding Reveals Lineage-dependent Outcomes in hiPSC Cardiac Differentiation.bioRxiv : the preprint server for biology · 2025Article
- Doblin: inferring dominant clonal lineages from high-resolution DNA barcoding time series.Bioinformatics (Oxford, England) · 2025Article
- A milestone for the therapeutic EV field: FDA approves Ryoncil, an allogeneic bone marrow-derived mesenchymal stromal cell therapy.Extracellular vesicles and circulating nucleic acids · 2025Article
- The Wnt pathway induces a naïve-like subpopulation in primed stem cells, while NME7AB leads to a homogeneous naïve-like population.PloS one · 2025Article
- Rethinking miRNAs in MSC-sEV therapeutics: implications for manufacture, mechanism of action, and development of robust potency CQAs.Extracellular vesicles and circulating nucleic acids · 2025Review
- Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head.Annals of medicine · 2024Review
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a functional assessment.Stem cell research & therapy · 2024Article
- Strategies in product engineering of mesenchymal stem cell-derived exosomes: unveiling the mechanisms underpinning the promotive effects of mesenchymal stem cell-derived exosomes.Frontiers in bioengineering and biotechnology · 2024Review
- How to differentiate induced pluripotent stem cells into sensory neurons for disease modelling: a comparison of two protocols.Research square · 2023Article
- iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs.International journal of molecular sciences · 2023Article
- The Evolving Landscape of Potency Assays.Advances in experimental medicine and biology · 2023Article
- Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation.BMC biology · 2022Article
- Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases.Stem cell research & therapy · 2022Review
- Phenotyping clonal populations of glioma stem cell reveals a high degree of plasticity in response to changes of microenvironment.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Longitudinal Monitoring of Intra-Tumoural Heterogeneity Using Optical Barcoding of Patient-Derived Colorectal Tumour Models.Cancers · 2022Article
- Ectopic Expression of FVIII in HPCs and MSCs Derived from hiPSCs with Site-Specific Integration ofInternational journal of molecular sciences · 2022Article
- Pluripotent-derived Mesenchymal Stem/stromal Cells: an Overview of the Derivation Protocol Efficacies and the Differences Among the Derived Cells.Stem cell reviews and reports · 2022Review
- Computational tools for analyzing single-cell data in pluripotent cell differentiation studies.Cell reports methods · 2021Review
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe use of mesenchymal stromal cells (MSCs) for research and clinical application is hampered by cellular heterogeneity and replicative senescence. Generation of MSC-like cells from induced pluripotent stem cells (iPSCs) may circumvent these limitations, and such iPSC-derived MSCs (iMSCs) are already tested in clinical trials. So far, a comparison of MSCs and iMSCs was particularly addressed in bulk culture. Despite the high hopes in cellular therapy, only little is known how the composition of different subclones changes in these cell preparations during culture expansion.
methodsIn this study, we used multicolor lentiviral genetic barcoding for the marking of individual cells within cell preparations. Based on this, we could track the clonal composition of syngenic MSCs, iPSCs, and iMSCs during culture expansion. Furthermore, we analyzed DNA methylation patterns at senescence-associated genomic regions by barcoded bisulfite amplicon sequencing. The proliferation and differentiation capacities of individual subclones within MSCs and iMSCs were investigated with limiting dilution assays.
resultsOverall, the clonal composition of primary MSCs and iPSCs gradually declined during expansion. In contrast, iMSCs became oligoclonal early during differentiation, indicating that they were derived from few individual iPSCs. This dominant clonal outgrowth of iMSCs was not associated with changes in chromosomal copy number variation. Furthermore, clonal dynamics were not clearly reflected by stochastically acquired DNA methylation patterns. Limiting dilution assays revealed that iMSCs are heterogeneous in colony formation and in vitro differentiation potential, while this was even more pronounced in primary MSCs.
conclusionsOur results indicate that the subclonal diversity of MSCs and iPSCs declines gradually during in vitro culture, whereas derivation of iMSCs may stem from few individual iPSCs. Differentiation regimen needs to be further optimized to achieve homogeneous differentiation of iPSCs towards iMSCs.
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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.