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胚胎腭骨发生的多模态时空转录组解析。

Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis.

机构信息

Section on Craniofacial Genetic Disorders, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.

出版信息

Nat Commun. 2023 Sep 14;14(1):5687. doi: 10.1038/s41467-023-41349-9.


DOI:10.1038/s41467-023-41349-9
PMID:37709732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10502152/
Abstract

The terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and nasal cavities. While the morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms driving the formation of this bony union of the fusing palate. Through bulk, single-nucleus, and spatially resolved RNA-sequencing analyses of the developing secondary palate, we identify a shift in transcriptional programming between embryonic days 14.5 and 15.5 pinpointing the onset of osteogenesis. We define spatially restricted expression patterns of key osteogenic marker genes that are differentially expressed between these developmental timepoints. Finally, we identify genes in the palate highly expressed by palate nasal epithelial cells, also enriched within palatal osteogenic mesenchymal cells. This investigation provides a relevant framework to advance palate-specific diagnostic and therapeutic biomarker discovery.

摘要

成骨细胞的终末分化和随后的骨形成标志着腭发育的重要阶段,导致口腔和鼻腔的分离。虽然腭成骨发生之前的形态发生事件已经得到了很好的研究,但我们对驱动融合腭骨性连接形成的分子机制的理解仍存在很大的差距。通过对发育中的次级腭的批量、单核和空间分辨 RNA 测序分析,我们确定了胚胎第 14.5 天和第 15.5 天之间转录编程的转变,指出了成骨作用的开始。我们定义了关键成骨标记基因的空间限制表达模式,这些基因在这些发育时间点之间的表达存在差异。最后,我们鉴定了腭中高度表达的基因,这些基因也在腭成骨间充质细胞中富集。这项研究提供了一个相关的框架,以推进腭特异性诊断和治疗生物标志物的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/d7aad96f7011/41467_2023_41349_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/683854660c68/41467_2023_41349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/05b671494582/41467_2023_41349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/24c2051658b8/41467_2023_41349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/462093c0b86e/41467_2023_41349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/d6ff8b58a3f1/41467_2023_41349_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/f0a3bdd4ce96/41467_2023_41349_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/d7aad96f7011/41467_2023_41349_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/683854660c68/41467_2023_41349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/05b671494582/41467_2023_41349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/24c2051658b8/41467_2023_41349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/462093c0b86e/41467_2023_41349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/d6ff8b58a3f1/41467_2023_41349_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/f0a3bdd4ce96/41467_2023_41349_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b2/10502152/d7aad96f7011/41467_2023_41349_Fig7_HTML.jpg

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[2]
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[3]
Leveraging Spatial Transcriptomics to Decode Craniofacial Development.

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[4]
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Bone Res. 2025-5-16

[5]
High-resolution spatial transcriptomics and cell lineage analysis reveal spatiotemporal cell fate determination during craniofacial development.

Nat Commun. 2025-5-12

[6]
Distinguishing syndromic and nonsyndromic cleft palate through analysis of protein-altering de novo variants in 816 trios.

medRxiv. 2025-3-4

[7]
A Single-cell Atlas of Developing Mouse Palates Reveals Cellular and Molecular Transitions in Periderm Cell Fate.

Genomics Proteomics Bioinformatics. 2025-5-10

[8]
Single Cell Spatial Transcriptomics of the Murine Embryonic Palate Links Pax9 to Patterning and Organization of Extracellular Matrix Components.

Res Sq. 2025-2-19

[9]
Gene expression patterns of the developing human face at single cell resolution reveal cell type contributions to normal facial variation and disease risk.

bioRxiv. 2025-2-5

[10]
Spatial Transcriptomics Unravel the Tissue Complexity of Oral Pathogenesis.

J Dent Res. 2024-12

本文引用的文献

[1]
LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility.

Elife. 2023-12-13

[2]
Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity.

Nat Commun. 2023-3-27

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Orthod Craniofac Res. 2023-2

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BMP4 Regulates EMT to be Involved in non-Syndromic Cleft lip With or Without Palate.

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J Dent Res. 2022-3

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LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice.

J Cell Sci. 2021-10-15

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