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Single-cell transcriptome profiling reveals developmental trajectory and regulatory networks of mouse maxillary prominence [RNA-seq]

ABSTRACT: The formation of maxillary prominence in vertebrates involves precisely coordinated migration and differentiation of neural crest cells. However, the regulatory factors and networks underpinning such an intricate process has not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 12.5, a critical period when a multitude of facial tissues start to emerge. We identified multiple cell populations that represent different developmental transition states and inferred the developmental trajectory of maxillary mesenchyme, revealing that a developmental bifurcation toward either an osteochondrogenic fate or a non-osteochondrogenic fate occurs at E11.5. We further deduced the core transcriptional regulators and gene regulatory networks associated with the maxillary cell fate transitions. Moreover, we revealed transcriptional regulators that are linked to dynamic changes in chromatin accessibility during maxillary development. Collectively, our study for the first time characterized the maxillary developmental process at single cell resolution, providing rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality.

ORGANISM(S): Mus musculus

PROVIDER: GSE161126 | GEO | 2023/11/30

REPOSITORIES: GEO

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Single-cell transcriptome profiling reveals developmental trajectory and regulatory networks of mouse maxillary prominence [ATAC-seq]

Project description:The formation of maxillary prominence in vertebrates involves precisely coordinated migration and differentiation of neural crest cells. However, the regulatory factors and networks underpinning such an intricate process has not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 12.5, a critical period when a multitude of facial tissues start to emerge. We identified multiple cell populations that represent different developmental transition states and inferred the developmental trajectory of maxillary mesenchyme, revealing that a developmental bifurcation toward either an osteochondrogenic fate or a non-osteochondrogenic fate occurs at E11.5. We further deduced the core transcriptional regulators and gene regulatory networks associated with the maxillary cell fate transitions. Moreover, we revealed transcriptional regulators that are linked to dynamic changes in chromatin accessibility during maxillary development. Collectively, our study for the first time characterized the maxillary developmental process at single cell resolution, providing rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality.

2023-11-30 | GSE161130 | GEO

Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

Project description:During embryonic development of vertebrates, neural crest- derived mesenchymal cells within the maxillary prominences undergo precisely coordinated proliferation and differentiation to give rise to a series of craniofacial structures, such as tooth and secondary palate. However, the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated. Here we combined bulk and single-cell RNA-Seq to comprehensively characterize the transcriptome dynamics during mouse maxillary development from embryonic day (E) 10.5 to 14.5. We identified mesenchymal cell populations that represent different developmental states and inferred their developmental trajectory, demonstrating that a cell fate divergence toward the palatal versus dental mesenchyme lineage occurs at E11.5. We further identified the core transcriptional regulators associated with maxillary cell fate transitions and deduced the gene regulatory networks directed by these factors. We further demonstrated that Foxp1 regulates genes involved in skeletal and cartilage development and is required for efficient osteogenesis. Collectively, our study provides rich resources and important insights for achieving a systems level understanding of craniofacial morphogenesis and abnormality.

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Single-cell transcriptome profiling reveals developmental trajectory and regulatory networks of mouse maxillary prominence

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Single-cell transcriptome profiling reveals developmental trajectory and transcriptional regulatory networks of mouse maxillary prominence

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Single-cell transcriptome profiling reveals developmental trajectory and regulatory networks of mouse maxillary prominence [RNA-seq]

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Single-cell transcriptome profiling reveals developmental trajectory and regulatory networks of mouse maxillary prominence

Project description:This SuperSeries is composed of the SubSeries listed below.

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A neural crest-specific overexpression mice model reveals the transcriptional regulatory effects of Dlx2 during maxillary process development

Project description:Craniofacial morphogenesis is an intricate process that requires precise regulation of cell proliferation, migration, and differentiation. Perturbations of this process cause a series of craniofacial deformities. Dlx2 is a critical transcription factor that regulates the development of the first branchial arch. However, the transcriptional regulatory functions of Dlx2 during craniofacial development have been poorly understood due to the lack of animal models in that the levels of Dlx2 can be precisely modulated. In this study, we constructed a Rosa26 site-directed Dlx2 gene knock-in mouse model Rosa26CAG-LSL-Dlx2-3xFlag for conditionally overexpressing Dlx2. By breeding with Wnt1cre mice, we obtained Wnt1cre; Rosa26Dlx2/- mice in which Dlx2 is overexpressed in neural crest lineage at about three times the endogenous level. The Wnt1cre; Rosa26Dlx2/- mice exhibited consistent phenotypes that include cleft palate across generations and individual animals. Using this model, we demonstrated that Dlx2 caused cleft palate by affecting maxillary growth in the early-stage development of maxillary prominences. By performing bulk RNA-seq, we demonstrated that the overexpression of Dlx2 induced significant changes of many genes related to critical developmental pathways. In summary, our novel mouse model provides a reliable and consistent system for investigating the functions of Dlx2 during development and for dissecting the gene regulatory networks underlying craniofacial development.

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