Single-cell multiomics decodes regulatory programs for mouse secondary palate development

Fangfang Yan, Akiko Suzuki, Chihiro Iwaya, Guangsheng Pei, Xian Chen, Hiroki Yoshioka, Meifang Yu, Lukas M. Simon (), Junichi Iwata () and Zhongming Zhao ()
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Fangfang Yan: The University of Texas Health Science Center at Houston
Akiko Suzuki: The University of Texas Health Science Center at Houston
Chihiro Iwaya: The University of Texas Health Science Center at Houston
Guangsheng Pei: The University of Texas Health Science Center at Houston
Xian Chen: The University of Texas Health Science Center at Houston
Hiroki Yoshioka: The University of Texas Health Science Center at Houston
Meifang Yu: The University of Texas Health Science Center at Houston
Lukas M. Simon: Baylor College of Medicine
Junichi Iwata: The University of Texas Health Science Center at Houston
Zhongming Zhao: The University of Texas Health Science Center at Houston

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45199-x

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