Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells

Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generat...

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Bibliographic Details
Published in:iScience 2024-04, Vol.27 (4), p.109585, Article 109585
Main Authors: Foltz, Lauren, Avabhrath, Nagashree, Lanchy, Jean-Marc, Levy, Tyler, Possemato, Anthony, Ariss, Majd, Peterson, Bradley, Grimes, Mark
Format: Article
Language:English
Subjects:
Biochemistry
Biological sciences
Cell biology
Natural sciences
Specialized functions of cells
Stem cells research
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Summary:Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generated self-organizing craniofacial cartilage organoids from human embryonic stem cell-derived neural crest stem cells. Histological staining of cartilage organoids revealed tissue architecture and staining typical of elastic cartilage. Protein and post-translational modification (PTM) mass spectrometry and snRNA-seq data showed that chondrocyte organoids expressed robust levels of cartilage extracellular matrix (ECM) components: many collagens, aggrecan, perlecan, proteoglycans, and elastic fibers. We identified two populations of chondroprogenitor cells, mesenchyme cells and nascent chondrocytes, and the growth factors involved in paracrine signaling between them. We show that ECM components secreted by chondrocytes not only create a structurally resilient matrix that defines cartilage, but also play a pivotal autocrine cell signaling role in determining chondrocyte fate. [Display omitted] •Craniofacial cartilage organoids were grown from human neural crest stem cells•These organoids exhibited elastic cartilage architecture and characteristic markers•Paracrine signaling drove chondrogenesis in mesenchyme cells and nascent chondrocytes•ECM components cemented chondrocyte cell fate through autocrine signaling Natural sciences; Biological sciences; Biochemistry; Cell biology; Stem cells research; Specialized functions of cells
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109585