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

Badam Enkhmandakh; Paul Robson; Pujan Joshi; Anushree Vijaykumar; Dong-Guk Shin; Mina Mina; Dashzeveg Bayarsaihan

doi:10.1155/2022/4969441

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

Stem Cells Int. 2022 Aug 12:2022:4969441. doi: 10.1155/2022/4969441. eCollection 2022.

Authors

Badam Enkhmandakh¹, Paul Robson², Pujan Joshi³, Anushree Vijaykumar⁴, Dong-Guk Shin³, Mina Mina⁴, Dashzeveg Bayarsaihan^{1

5}

Affiliations

¹ Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
² The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
³ Computer Science and Engineering Department, University of Connecticut, 371 Fairfield Way, Unit 4155, Storrs, CT 06269, USA.
⁴ Department of Craniofacial Sciences, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
⁵ Institute for System Genomics, University of Connecticut, Engineering Science Building Rm. 305, 67 North Eagleville Road, Storrs, CT 06269, USA.

Abstract

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.

Abstract

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