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Published October 25, 2023 | Published
Journal Article Open

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

  • 1. ROR icon California Institute of Technology


During development, much of the enteric nervous system (ENS) arises from the vagal neural crest that emerges from the caudal hindbrain and colonizes the entire gastrointestinal tract. However, a second ENS contribution comes from the sacral neural crest that arises in the caudal neural tube and populates the post-umbilical gut. By coupling single-cell transcriptomics with axial-level-specific lineage tracing in avian embryos, we compared the contributions of embryonic vagal and sacral neural crest cells to the chick ENS and the associated peripheral ganglia (Nerve of Remak and pelvic plexuses). At embryonic day (E) 10, the two neural crest populations form overlapping subsets of neuronal and glia cell types. Surprisingly, the post-umbilical vagal neural crest much more closely resembles the sacral neural crest than the pre-umbilical vagal neural crest. However, some differences in cluster types were noted between vagal and sacral derived cells. Notably, RNA trajectory analysis suggests that the vagal neural crest maintains a neuronal/glial progenitor pool, whereas this cluster is depleted in the E10 sacral neural crest which instead has numerous enteric glia. The present findings reveal sacral neural crest contributions to the hindgut and associated peripheral ganglia and highlight the potential influence of the local environment and/or developmental timing in differentiation of neural crest-derived cells in the developing ENS.

Copyright and License

© 2023, Jacobs-Li, Tang et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


This work was supported by 1R01DK133480 to MEB and F31 HD111287 to JLL We thank Drs. Igor Antoshechkin and Vijaya Kumar and the Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology for their guidance and support in bulk RNA-sequencing. We thank Jamie Tijerina and Rochelle Diamond from the Beckman Institute Flow Cytometry Facility for their help with the FACS. We thank Dr. Sisi Chen, Jeff Park, Prof. Matt Thomson, and SPEC at Caltech for their dedicated support in optimization and guidance in single-cell RNA-sequencing. We thank Dr. Fan Gao and Bioinformatics Resource Center in the Beckman Institute at Caltech for guiding us through single-cell transcriptomic analysis. We appreciate the help from Prof. Carlos Lois for kindly sharing equipment with us to perform RIA concentration. We thank Dr. Michael L Piacentino, Dr. Erica J Hutchins, and Prof. Angelike Stathopoulos for the helpful discussion on the manuscript.


Jessica Jacobs-Li, Data curation, Formal analysis, Validation, Writing - review and editing; Weiyi Tang, Conceptualization, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review and editing; Can Li, Formal analysis, Methodology; Marianne E Bronner, Conceptualization, Resources, Funding acquisition, Writing - original draft, Project administration, Writing - review and editing

Conflict of Interest

Marianne E Bronner: Senior editor, eLife. The other authors declare that no competing interests exist.

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


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Additional details

November 9, 2023
January 9, 2024