Evidence map›Paper›PMID 39407288›Full record

ArticleClinical epigenetics2024

The role of DNA methylation in chondrogenesis of human iPSCs as a stable marker of cartilage quality.

Ghazaleh Hajmousa, Rodrigo Coutinho de Almeida, Niek Bloks, Alejandro Rodríguez Ruiz, Marga Bouma, Roderick Slieker, Thomas B Kuipers, Rob G H H Nelissen, Keita Ito, Christian Freund and 2 more

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Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ghazaleh Hajmousa *Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Rodrigo Coutinho de Almeida *Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Niek Bloks *Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Alejandro Rodríguez RuizDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Marga BoumaDepartment of Anatomy and Embryology and Human iPSC Hotel, 2333 ZA, Leiden, The Netherlands.
Roderick SliekerDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Thomas B KuipersDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Rob G H H NelissenDepartment of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands.
Keita ItoOrthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, The Netherlands.
Christian FreundDepartment of Anatomy and Embryology and Human iPSC Hotel, 2333 ZA, Leiden, The Netherlands.
Yolande F M RamosDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Ingrid MeulenbeltDepartment of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Post-zone S-05-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. I.Meulenbelt@lumc.nl.ORCID http://orcid.org/0000-0001-7786-7081

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLack of insight into factors that determine purity and quality of human iPSC (hiPSC)-derived neo-cartilage precludes applications of this powerful technology toward regenerative solutions in the clinical setting. Here, we set out to generate methylome-wide landscapes of hiPSC-derived neo-cartilages from different tissues-of-origin and integrated transcriptome-wide data to identify dissimilarities in set points of methylation with associated transcription and the respective pathways in which these genes act.

methodsWe applied in vitro chondrogenesis using hiPSCs generated from two different tissue sources: skin fibroblasts and articular cartilage. Upon differentiation toward chondrocytes, these are referred to as hFiCs and hCiC, respectively. Genome-wide DNA methylation and RNA sequencing datasets were generated of the hiPSC-derived neo-cartilages, and the epigenetically regulated transcriptome was compared to that of neo-cartilage deposited by human primary articular cartilage (hPAC).

resultsMethylome-wide landscapes of neo-cartilages of hiPSCs reprogrammed from two different somatic tissues were 85% similar to that of hPACs. By integration of transcriptome-wide data, differences in transcriptionally active CpGs between hCiC relative to hPAC were prioritized. Among the CpG-gene pairs lower expressed in hCiCs relative to hPACs, we identified genes such as MGP, GDF5, and CHAD enriched in closely related pathways and involved in cartilage development that likely mark phenotypic differences in chondrocyte states. Vice versa, among the CpG-gene pairs higher expressed, we identified genes such as KIF1A or NKX2-2 enriched in neurogenic pathways and likely reflecting off target differentiation.

conclusionsWe did not find significant variation between the neo-cartilages derived from hiPSCs of different tissue sources, suggesting that application of a robust differentiation protocol such as we applied here is more important as compared to the epigenetic memory of the cells of origin. Results of our study could be further exploited to improve quality, purity, and maturity of hiPSC-derived neo-cartilage matrix, ultimately to realize introduction of sustainable, hiPSC-derived neo-cartilage implantation into clinical practice.

Indexed as

Cartilage, ArticularCell DifferentiationChondrogenesisDNA MethylationEpigenesis, GeneticInduced Pluripotent Stem CellsCells, CulturedChondrocytesCpG IslandsFibroblastsHomeobox Protein Nkx-2.2HumansTranscriptomeHomeobox Protein Nkx-2.2hiPSCsMethylationNeo-cartilageRegenerationTranscriptional set points

Identifiers

PMID39407288
PMCPMC11481477

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Registered trials

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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.