Single-cell transcriptome analysis defines mesenchymal stromal cells in the mouse incisor dental pulp

Bayarsaihan, Dashzeveg; Enkhmandakh, Badam; Vijaykumar, Anushree; Robson, Paul; Mina, Mina

doi:10.1016/j.gep.2021.119228

Cited by 7 publications

(9 citation statements)

References 24 publications

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“…We previously identified several clusters of MSCs in the mouse incisor dental pulp that represent subpopulations of osteogenic cells at different stages of differentiation (Bayarsaihan et al, 2022). These MSCs express a wide range of genes including Msx1, Snai1, Dlx1, Twist2, and Tfap2a, that are important for differentiation of the neural crest, osteogenic, and chondrogenic lineages (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…We previously identified 16 distinct cell clusters in the dental pulp of mouse incisors based on the differential expression of marker genes (Bayarsaihan et al, 2022). According to the expression of key genes required for osteogenic differentiation, we identified eight clusters of MSCs (Fig.…”

Section: Single-cell Rna Expression Of Sox Genes In Different Cell Su...mentioning

confidence: 99%

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Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp

Enkhmandakh¹,

Bayarsaihan²

2023

Int. J. Dev. Biol.

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SOX transcription factors play key roles in cell differentiation and cell fate determination during development. Using single-cell RNA-sequencing data, we examined the expression profiles of Sox genes in the mouse incisor dental pulp. Our analysis showed that Sox4, Sox5, Sox9, Sox11, and Sox12 are mainly expressed in mesenchymal stem/stromal cells (MSCs) representing osteogenic cells at different stages of differentiation. We found that in several MSCs, Sox genes co-expressed with regulatory genes such as Sp7, Satb2, Msx1, Snai2, Dlx1, Twist2, and Tfap2a. In addition, Sox family genes colocalized with Runx2 and Lef1, which are highly enriched in MSCs undergoing osteoblast differentiation. A protein interaction network analysis uncovered that CREBBP, CEBPB, TLE1, TWIST1, and members of the HDAC and SMAD families are interacting partners of RUNX2 and LEF1 during skeletal development. Collectively, the distinct expression patterns of the SOX transcription factors suggest that they play essential regulatory roles in directing lineage-specific gene expression during differentiation of MSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Single-cell Rna Expression Of Sox Genes In Different Cell Su...mentioning

confidence: 99%

Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp

Enkhmandakh¹,

Bayarsaihan²

2023

Int. J. Dev. Biol.

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“…Our study revealed that genes encoding KMT2D and KDM6A and other components of the SET1/COMPASS activation complex display overlapping expression patterns within the mouse dental pulp. Sixteen clusters of cells represent MSCs at different stages of osteogenic and odontogenic differentiation as well as pericytes, ameloblasts, smooth muscle cells, islet cells, Schwann cells, vascular endothelial cells, and blood cells [17]. We identified a core set of genes that are common in clusters 1, 2, 3, 8, and 9, which represent the five subpopulations of MSCs (Figure 5).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, using single-cell RNA sequencing (scRNAseq), we characterized the cellular composition of the mouse incisor dental pulp [17]. Our study revealed distinct patterns of cell state heterogeneity in mesenchymal stem/stromal cells (MSCs) undergoing different stages of differentiation, including differentiated cells representing osteoblasts and odontoblasts.…”

Section: Introductionmentioning

confidence: 92%

“…The STRING analysis revealed that enhancer of zeste homolog 2 (EZH2) and suppressor of zeste 12 protein homolog (SUZ12), key components of the polycomb repressive complex 2 (PRC2), physically interact with KMT2D and KDM6A. Previously, we reported the results of an scRNA-seq analysis to define the expression pattern of developmental genes in the incisor dental pulp [17]. Based on the expression of key genes, we grouped the pulp cells into 16 clusters (Figure 1 3).…”

Section: Expression Of Members Of the Set1/compass And Prc2mentioning

confidence: 99%

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Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners

Enkhmandakh

Robson

Joshi

et al. 2022

Stem Cells International

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Objectives. Kabuki syndrome (KS) is a rare genetic disorder characterized by developmental delay, retarded growth, and cardiac, gastrointestinal, neurocognitive, renal, craniofacial, dental, and skeletal defects. KS is caused by mutations in the genes encoding histone H3 lysine 4 methyltransferase (KMT2D) and histone H3 lysine 27 demethylase (KDM6A), which are core components of the complex of proteins associated with histone H3 lysine 4 methyltransferase SET1 (SET1/COMPASS). Using single-cell RNA data, we examined the expression profiles of Kmt2d and Kdm6a in the mouse dental pulp. In the incisor pulp, Kmt2d and Kdm6a colocalize with other genes of the SET1/COMPASS complex comprised of the WD-repeat protein 5 gene (Wdr5), the retinoblastoma-binding protein 5 gene (Rbbp5), absent, small, and homeotic 2-like protein-encoding gene (Ash2l), nuclear receptor cofactor 6 gene (Ncoa6), and Pax-interacting protein 1 gene (Ptip1). In addition, we found that Kmt2d and Kdm6a coexpress with the downstream target genes of the Wingless and Integrated (WNT) and sonic hedgehog signaling pathways in mesenchymal stem/stromal cells (MSCs) at different stages of osteogenic differentiation. Taken together, our results suggest an essential role of KMT2D and KDK6A in directing lineage-specific gene expression during differentiation of MSCs.

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Single‐cell RNA analysis of chromodomain‐encoding genes in mesenchymal stromal cells of the mouse dental pulp

Becker,

Enkhmandakh,

Bayarsaihan

2024

J of Cellular Biochemistry

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The chromodomain helicase DNA‐binding (CHD) and chromobox (CBX) families of proteins play crucial roles in cell fate decisions, differentiation, and cell proliferation in a broad variety of tissues and cell types. CHD proteins are ATP‐dependent epigenetic enzymes actively engaged in transcriptional regulation, DNA replication, and DNA damage repair, whereas CBX proteins are transcriptional repressors mainly involved in the formation of heterochromatin. The pleiotropic effects of CHD and CBX proteins are largely dependent on their versatility to interact with other key components of the epigenetic and transcriptional machinery. Although the function and regulatory modes of CHD and CBX factors are well established in many cell types, little is known about their roles during osteogenic differentiation. A single‐cell RNA‐sequencing analysis of the mouse incisor dental pulp revealed distinct spatiotemporal expression patterns of CHD‐ and CBX‐encoding genes within different clusters of mesenchymal stromal cells (MSCs) representing various stages of osteogenic differentiation. Additionally, genes encoding interaction partners of CHD and CBX proteins, such as subunits of the trithorax‐COMPASS and polycomb chromatin remodeling complexes, exhibited differential co‐expression behaviors within MSC subpopulations. Thus, CHD‐ and CBX‐encoding genes show partially overlapping but distinct expression patterns in MSCs, suggesting their differential roles in osteogenic cell fate decisions.

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Single-cell transcriptome analysis defines mesenchymal stromal cells in the mouse incisor dental pulp

Cited by 7 publications

References 24 publications

Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp

Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp

Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners

Single‐cell RNA analysis of chromodomain‐encoding genes in mesenchymal stromal cells of the mouse dental pulp

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