Comparison of cardiogenic potential of induced Pluripotent Stem Cells (iPSCs) generated from murine various tissues: the role of epigenetic memory in reprogramming
Notice bibliographique
Résumé
Introduction Coronary artery disease (CAD), i.e. myocardial infarction and ischemic cardiomyopathy, is the global leading cause of death. Ischemia leads to loss of functional cardiomyocytes, which contributes to a variety of types of heart failure. Although conventional treatments including pharmacological therapy and coronary revascularization procedures exist, novel therapeutic approaches are still needed. The prospect of stem‐cell‐based therapies might have considerable therapeutic potential. Induced pluripotent stem cells (iPSCs) can be generated from a variety of somatic cells as a potential resource of replacement cells, making them ideal cellular models to provide a renewable source of cardiomyocytes for cell‐based therapy. However, an ideal cell type with superior cardiomyocyte (CM) potential has yet to be identified. Masseter muscle cells (MMC) characterized as Isl‐1 + cells, a genetic marker associated with stem and progenitor states, also contribute to various cardiovascular lineages and have similar embryological origins. We postulate the regenerative potential of masseter muscle cell lineages may yield valuable developmental and clinical insights in the identification of a cell source capable of enhanced cardiomyocyte differentiation and may be used in cell‐based therapy. This study aims to study the role of epigenetic memory in the cardiogenic potential of different lineages of iPSC. Methods A variety of cell sources including masseter muscle cells (MMC), dermal fibroblasts (Fib), bone marrow mesenchymal cells (BMC), and Trunk skeletal muscle cells (TMC) from mouse were isolated. These cell sources were then transfected with Yamanaka's factors (Oct4, Sox2, c‐Myc, and Klf‐4) to generate four lineages of iPSCs. These four iPSC cell lineages were differentiated into iPSC‐CMs via 3‐D culture protocols and analyzed for differences in their differentiation potential as well as the efficiency of differentiation. Cardiomyocytes differentiation was analyzed by spontaneous contractions, immunostaining, flow cytometry test, and patch clamp. The epigenetic signatures of somatic cells, iPSCs, and derived Cardiomyocytes were analyzed by Real‐time PCR. Methylation study was used to evaluate epigenetic memory of four lineages of iPSCs. Results Spontaneous beating was observed in 80% colonies of MMC‐derived iPSC‐cardiomyocytes (MMC‐CM), which was significantly higher than other groups. Cardiac genes Isl‐1, Nkx2.5, and GATA4 were also significantly upregulated in MMC‐CM. MMC‐CM exerted robust cardiac functional phenotype, indicated by enhanced contractility and electrophysiological properties. Low methylation levels of the cardiac mesodermal gene (Isl‐1) in MMC and M‐iPSC were similar to neonatal cardiomyocytes and were maintained in MMC‐CM. Cardiac genes were epigenetically silenced in other somatic cells. Conclusion iPSCs derived from masseter muscle cell sources have better cardiogenic differentiation capabilities than other somatic cell sources. Epigenetic memory significantly contributes to the prominent cardiogenic potential of masseter‐derived iPSCs. Support or Funding Information National Institutes of Health grants (HL110740)
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».