Single-Cell Multiomics Decodes Regulatory Programs for Mouse Secondary Palate Development

Authors

Fangfang Yan
Akiko Suzuki
Chihiro Iwaya
Guangsheng Pei
Xian Chen
Hiroki Yoshioka
Meifang Yu
Lukas M Simon
Junichi Iwata
Zhongming Zhao

Publication Date

1-27-2024

Journal

Nature Communications

Abstract

Perturbations in gene regulation during palatogenesis can lead to cleft palate, which is among the most common congenital birth defects. Here, we perform single-cell multiome sequencing and profile chromatin accessibility and gene expression simultaneously within the same cells (n = 36,154) isolated from mouse secondary palate across embryonic days (E) 12.5, E13.5, E14.0, and E14.5. We construct five trajectories representing continuous differentiation of cranial neural crest-derived multipotent cells into distinct lineages. By linking open chromatin signals to gene expression changes, we characterize the underlying lineage-determining transcription factors. In silico perturbation analysis identifies transcription factors SHOX2 and MEOX2 as important regulators of the development of the anterior and posterior palate, respectively. In conclusion, our study charts epigenetic and transcriptional dynamics in palatogenesis, serving as a valuable resource for further cleft palate research.

Keywords

Differentiation, Computational biology and bioinformatics, Cell lineage

Comments

Supplementary Materials

PMID: 38280850