Research Seminar Series: Lifelong Single-Cell Profiling of Cranial Neural Crest Diversification
Presented by Gage Crump, PhD
Professor, Stem Cell Biology & Regenerative Medicine
Keck School of Medicine of USC
Talk Summary: The cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. Rather than multilineage potential being an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse lineage potential.
About the Speaker: Gage Crump has made a career of using genetics and in vivo imaging to understand how complex organs are assembled. During my PhD, I performed some of the first GFP-based forward genetic screens to uncover molecules essential for correct synaptic choice in C. elegans. In so doing, I discovered a new family of SAD protein kinases required for synapse assembly and neuronal polarity (Neuron), and then collaborated with Joshua Sanes to show a conserved function of these kinases in mammals (Science). During my postdoc, I developed single-cell lineage techniques and in vivo time-lapse microscopy in zebrafish to make the first fate map of the vertebrate facial skeleton. As a founding member of the Broad Stem Cell Center at USC, I have expanded my research program to study the maintenance and regeneration of the adult craniofacial skeleton. I have also taken a leading role in establishing the relevance of our zebrafish findings to the human condition. To do so, I have formed a broad collaborative network with mammalian researchers and clinicians throughout USC, which is reflected by several collaborative grants and publications. Our unique efforts in validating zebrafish discoveries in mammalian models show our commitment to one day translating our basic research findings into new regenerative medicine approaches for musculoskeletal defects and disease.
Hosted by James Amatruda, MD, PhD
Professor of Pediatrics and Medicine
Keck School of Medicine of USC
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