Publication Date

2-7-2023

Journal

Proceedings of the National Academy of Sciences of the United States of America

DOI

10.1073/pnas.2212578120

PMID

36724256

PMCID

PMC9963983

PubMedCentral® Posted Date

2-1-2023

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Cell Differentiation, Chromatin, Gene Expression Regulation, Developmental, MicroRNAs, Neural Crest, RNA Processing, Post-Transcriptional, multipotency, pluripotency, single-cell, microRNAs, chromatin accessibility

Abstract

Developmental potential is progressively restricted after germ layer specification during gastrulation. However, cranial neural crest cells challenge this paradigm, as they develop from anterior ectoderm, yet give rise to both ectodermal derivatives of the peripheral nervous system and ectomesenchymal bone and cartilage. How cranial neural crest cells differentiate into multiple lineages is poorly understood. Here, we demonstrate that cranial neural crest cells possess a transient state of increased chromatin accessibility. We profile the spatiotemporal emergence of premigratory neural crest and find evidence of lineage bias toward either a neuronal or ectomesenchymal fate, with each expressing distinct factors from earlier stages of development. We identify the miR-302 miRNA family to be highly expressed in cranial neural crest cells and genetic deletion leads to precocious specification of the ectomesenchymal lineage. Loss of

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