Genomic mosaicism reveals developmental organization of trunk neural crest-derived ganglia.

Autor: Vong KI; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.; These authors contributed equally., Alvarez YD; Institute for Molecular Biosciences, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia., Noel G; Division of Medical Education, School of Medicine, University of California San Diego, La Jolla, CA 92037, USA., Barton ST; Division of Medical Education, School of Medicine, University of California San Diego, La Jolla, CA 92037, USA., Chung C; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Howarth R; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Meave N; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Zhang Q; Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA., Jiwani F; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Barrows C; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Patel A; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., Wang JX; Institute for Molecular Biosciences, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia., Chi N; Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.; Department of Bioengineering, University of California San Diego, La Jolla, CA 92037, USA.; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92037, USA.; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92037, USA., Kingsmore SF; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA., White MD; Institute for Molecular Biosciences, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia., Yang X; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.; Utah Center for Genetic Discovery, Salt Lake City, UT 84112, USA.; These authors contributed equally., Gleeson JG; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.; Lead contact.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 26. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1101/2024.09.25.615004
Abstrakt: The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.
Databáze: MEDLINE