Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds.

Animals Benzoates / pharmacology Cartilage / metabolism Cell Differentiation / drug effects Chondrocytes / cytology Chondrogenesis Chromatin / metabolism Collagen Type X / genetics Gene Expression Humans Mice Mice, Inbred NOD Pluripotent Stem Cells / cytology Pyridines / pharmacology Pyrimidines / pharmacology Receptors, Retinoic Acid / genetics Retinoids / pharmacology Wnt Signaling Pathway beta Catenin / genetics
cartilage chondrocyte chondrocyte differentiation pluripotent stem cells regenerative medicine small-molecule compound

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
10 09 2019
Historique:
received: 27 01 2019
revised: 15 07 2019
accepted: 16 07 2019
pubmed: 14 8 2019
medline: 19 6 2020
entrez: 13 8 2019
Statut: ppublish

Résumé

A simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that chondrocytes are robustly induced from human PSCs by simple combination of two compounds, CHIR99021, a glycogen synthase kinase 3 inhibitor, and TTNPB, a retinoic acid receptor (RAR) agonist, under serum- and feeder-free conditions within 5-9 days. An excellent differentiation efficiency and potential to form hyaline cartilaginous tissues in vivo were demonstrated. Comprehensive gene expression and open chromatin analyses at each protocol stage revealed step-by-step differentiation toward chondrocytes. Genome-wide analysis of RAR and β-catenin association with DNA showed that retinoic acid and Wnt/β-catenin signaling collaboratively regulated the key marker genes at each differentiation stage. This method provides a promising cell source for regenerative medicine and, as an in vitro model, may facilitate elucidation of the molecular mechanisms underlying chondrocyte differentiation.

Identifiants

DOI: 10.1016/j.stemcr.2019.07.012 PMID: 31402337 PMC: PMC6739881
pubmed: 31402337
pii: S2213-6711(19)30264-4
doi: 10.1016/j.stemcr.2019.07.012
pmc: PMC6739881
pii:
doi:

Substances chimiques

Benzoates 0
Chir 99021 0
Chromatin 0
Collagen Type X 0
Pyridines 0
Pyrimidines 0
Receptors, Retinoic Acid 0
Retinoids 0
beta Catenin 0
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid 71441-28-6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

530-544

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Manabu Kawata (M)

Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Daisuke Mori (D)

Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Kosuke Kanke (K)

Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Hironori Hojo (H)

Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Shinsuke Ohba (S)

Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Ung-Il Chung (UI)

Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Fumiko Yano (F)

Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Hideki Masaki (H)

Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Makoto Otsu (M)

Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Hiromitsu Nakauchi (H)

Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Sakae Tanaka (S)

Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Taku Saito (T)

Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Bone and Cartilage Regenerative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: tasaitou-tky@umin.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Benzoates › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Tissus › Tissu conjonctif › Cartilage › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Chondrocytes › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Chondrogenèse › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes non fibrillaires › Collagène de type X › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs à l'acide rétinoïque › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Caroténoïdes › Rétinoïdes › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Simple and Robust Differentiation of Human...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Simple and Robust Differentiation of Human...