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高分辨率空间转录组学和细胞谱系分析揭示了颅面发育过程中的时空细胞命运决定。

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

作者信息

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

机构信息

Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California, 90033, USA.

出版信息

Nat Commun. 2025 May 12;16(1):4396. doi: 10.1038/s41467-025-59206-2.

DOI:10.1038/s41467-025-59206-2
PMID:40355462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069723/
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.

摘要

迁移后的颅神经嵴细胞（CNCCs）分化为不同的间充质谱系对于颅面发育至关重要。在此，我们报告了小鼠腭发生过程中CNCC衍生的间充质谱系多样化的高分辨率时空转录组学和细胞类型图谱。我们通过将每个间充质细胞类型的转录组谱映射到空间身份来系统地定义它们。对E12.5至E15.5的空间转录组数据的综合分析进一步揭示了腭发生开始时或之前的间充质谱系建立。我们还在腭发育开始时鉴定出一个异质性的Sox9+间充质祖细胞群体，其亚群已经激活早期谱系特异性标记。使用这些早期谱系特异性标记进行的体内谱系追踪表明，早在E10.5至E11.5，在腭发育之前就已建立了不同的间充质群体，并对它们各自的谱系做出贡献。总之，我们的发现揭示了腭发育的全面、动态分子和细胞景观，并为胚胎发生过程中的细胞命运调控提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/5f8b92954301/41467_2025_59206_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/50b5fdebb587/41467_2025_59206_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/3d2c68548792/41467_2025_59206_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/d76dcd0bdf32/41467_2025_59206_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/8fbc91f242de/41467_2025_59206_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/7511221803c4/41467_2025_59206_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/e2ea878d5ac2/41467_2025_59206_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/c991fc540f6f/41467_2025_59206_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/d5e238a82b6c/41467_2025_59206_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/6101ac60b9f7/41467_2025_59206_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/5f8b92954301/41467_2025_59206_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/50b5fdebb587/41467_2025_59206_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/3d2c68548792/41467_2025_59206_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/d76dcd0bdf32/41467_2025_59206_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/8fbc91f242de/41467_2025_59206_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/7511221803c4/41467_2025_59206_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/e2ea878d5ac2/41467_2025_59206_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/c991fc540f6f/41467_2025_59206_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/d5e238a82b6c/41467_2025_59206_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/6101ac60b9f7/41467_2025_59206_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a235/12069723/5f8b92954301/41467_2025_59206_Fig10_HTML.jpg

相似文献

[1]
High-resolution spatial transcriptomics and cell lineage analysis reveal spatiotemporal cell fate determination during craniofacial development.

Nat Commun. 2025-5-12

[2]
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[3]
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[4]
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[5]
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Dev Biol. 2018-9-14

[6]
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[7]
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[8]
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PLoS One. 2016-4-8

[9]
Reactivation of the pluripotency program precedes formation of the cranial neural crest.

Science. 2021-2-5

[10]
MEMO1 drives cranial endochondral ossification and palatogenesis.

Dev Biol. 2016-7-15

本文引用的文献

[1]
Single-cell multiomics decodes regulatory programs for mouse secondary palate development.

Nat Commun. 2024-1-27

[2]
Generation of tamoxifen-inducible Tfap2b-CreER mice using CRISPR-Cas9.

Genesis. 2024-2

[3]
A mouse model with high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells.

Cell. 2023-11-9

[4]
Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis.

Nat Commun. 2023-9-14

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Nat Biotechnol. 2024-2

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ScRNA-Seq Reveals a Distinct Osteogenic Progenitor of Alveolar Bone.

J Dent Res. 2023-6

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Heliyon. 2023-4-17

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Nat Rev Genet. 2023-8

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Single cell sequencing of the mouse anterior palate reveals mesenchymal heterogeneity.

Dev Dyn. 2023-6

[10]
In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis.

Nat Commun. 2023-1-3

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