A Single-cell Atlas of Developing Mouse Palates Reveals Cellular and Molecular Transitions in Periderm Cell Fate

TL;DR

This study uses single-cell RNA sequencing to map mouse palate development, revealing periderm cell subtypes and their molecular roles in palate formation.

Contribution

The study identifies four periderm subclusters and two fate trajectories, along with key genes involved in their differentiation and function.

Findings

Four subclusters of palatal periderm cells were identified using single-cell RNA sequencing.

Claudin-family genes and Arhgap29 are involved in periderm non-stick function before palate shelf contact.

Epithelial–mesenchymal transition, apoptosis, and migration contribute to periderm cell degeneration.

Abstract

Cleft palate is one of the most common congenital craniofacial disorders that affects children’s appearance and oral functions. Investigating the transcriptomes during palatogenesis is crucial for understanding the etiology of this disorder and facilitating prenatal molecular diagnosis. However, there is limited knowledge about the single-cell differentiation dynamics during mid-palatogenesis and late-palatogenesis, specifically regarding the subpopulations and developmental trajectories of periderm, a rare but critical cell population. Here, we explored the single-cell landscape of mouse developing palates from embryonic day (E) 10.5 to E16.5. We systematically depicted the single-cell transcriptomes of mesenchymal and epithelial cells during palatogenesis, including subpopulations and differentiation dynamics. Additionally, we identified four subclusters of palatal periderm and constructed two distinct trajectories of cell fates for periderm cells. Our findings reveal that claudin-family coding genes and Arhgap29 play a role in the non-stick function of the periderm before the palatal shelves contact, and Pitx2 mediates the adhesion of periderm during the contact of opposing palatal shelves. Furthermore, we demonstrate that epithelial–mesenchymal transition (EMT), apoptosis, and migration collectively contribute to the degeneration of periderm cells in the medial epithelial seam. Taken together, our study suggests a novel model of periderm development during palatogenesis and delineates the cellular and molecular transitions in periderm cell determination.

Graphical Abstract

Highlights
 • Single-cell RNA sequencing of developing mouse palates identified four subclusters of palatal periderm cells.• Two distinct fate trajectories of palatal periderm cells were identified.• Key molecules involved in periderm cell differentiation were revealed.• The mode of contact between periderm cells may determine the fate of periderm cells.

• Single-cell RNA sequencing of developing mouse palates identified four subclusters of palatal periderm cells.

• Two distinct fate trajectories of palatal periderm cells were identified.

• Key molecules involved in periderm cell differentiation were revealed.

• The mode of contact between periderm cells may determine the fate of periderm cells.

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