High-resolution spatial transcriptomics and cell lineage analysis reveal spatiotemporal cell fate determination during craniofacial development

Jifan Feng, Eva Janečková, Tingwei Guo, Heliya Ziaei, Mingyi Zhang, Jessica Junyan Geng, Sa Cha, Angelita Araujo-Villalba, Mengmeng Liu, Thach-Vu Ho and Yang Chai ()
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Jifan Feng: Los Angeles
Eva Janečková: Los Angeles
Tingwei Guo: Los Angeles
Heliya Ziaei: Los Angeles
Mingyi Zhang: Los Angeles
Jessica Junyan Geng: Los Angeles
Sa Cha: Los Angeles
Angelita Araujo-Villalba: Los Angeles
Mengmeng Liu: Los Angeles
Thach-Vu Ho: Los Angeles
Yang Chai: Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract The differentiation of post-migratory cranial neural crest cells (CNCCs) into distinct mesenchymal lineages is crucial for craniofacial development. Here we report a high-resolution spatiotemporal transcriptomic and cell-type atlas of CNCC-derived mesenchymal lineage diversification during mouse palatogenesis. We systematically defined each mesenchymal cell type by mapping their transcriptomic profiles to spatial identities. Integrative analysis of spatial transcriptomic data from E12.5 to E15.5 further revealed mesenchymal lineage establishment at or prior to initiation of palatogenesis. We also identified a heterogeneous Sox9+ mesenchymal progenitor population at the onset of palatal development, with subpopulations already activating early lineage-specific markers. In vivo lineage tracing using these early lineage-specific markers demonstrated that distinct mesenchymal populations are established as early as E10.5 to E11.5, preceding palatal development, and contribute to their respective lineages. Together, our findings reveal the comprehensive, dynamic molecular and cellular landscape of palate development and shed light on cell fate regulation during embryogenesis.

Date: 2025
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DOI: 10.1038/s41467-025-59206-2

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