Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells
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 tha...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224008071 |
| _version_ | 1797213368200724480 |
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| author | Lauren Foltz Nagashree Avabhrath Jean-Marc Lanchy Tyler Levy Anthony Possemato Majd Ariss Bradley Peterson Mark Grimes |
| author_facet | Lauren Foltz Nagashree Avabhrath Jean-Marc Lanchy Tyler Levy Anthony Possemato Majd Ariss Bradley Peterson Mark Grimes |
| author_sort | Lauren Foltz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T10:57:10Z |
| format | Article |
| id | doaj.art-23015d337b934de4b9abaaaf6113fc78 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T10:57:10Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-23015d337b934de4b9abaaaf6113fc782024-04-12T04:45:41ZengElsevieriScience2589-00422024-04-01274109585Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cellsLauren Foltz0Nagashree Avabhrath1Jean-Marc Lanchy2Tyler Levy3Anthony Possemato4Majd Ariss5Bradley Peterson6Mark Grimes7Division of Biological Sciences, Center for Biomolecular Structure and Dynamics, Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, USADivision of Biological Sciences, Center for Biomolecular Structure and Dynamics, Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, USADivision of Biological Sciences, Center for Biomolecular Structure and Dynamics, Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, USACell Signaling Technology, Danvers, MA 01923, USACell Signaling Technology, Danvers, MA 01923, USACell Signaling Technology, Danvers, MA 01923, USAPathology Consultants of Western Montana, Missoula, MT, USADivision of Biological Sciences, Center for Biomolecular Structure and Dynamics, Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224008071Natural sciencesBiological sciencesBiochemistryCell biologyStem cells researchSpecialized functions of cells |
| spellingShingle | Lauren Foltz Nagashree Avabhrath Jean-Marc Lanchy Tyler Levy Anthony Possemato Majd Ariss Bradley Peterson Mark Grimes Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells iScience Natural sciences Biological sciences Biochemistry Cell biology Stem cells research Specialized functions of cells |
| title | Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells |
| title_full | Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells |
| title_fullStr | Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells |
| title_full_unstemmed | Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells |
| title_short | Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells |
| title_sort | craniofacial chondrogenesis in organoids from human stem cell derived neural crest cells |
| topic | Natural sciences Biological sciences Biochemistry Cell biology Stem cells research Specialized functions of cells |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224008071 |
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