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

Lauren Foltz, Nagashree Avabhrath, Jean Marc Lanchy, Tyler Levy, Anthony Possemato, Majd Ariss, Bradley Peterson, Mark Grimes

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number109585
Pages (from-to)109585
JournaliScience
Volume27
Issue number4
DOIs
StatePublished - Apr 19 2024

Keywords

  • Biochemistry
  • Biological sciences
  • Cell biology
  • Natural sciences
  • Specialized functions of cells
  • Stem cells research

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