The International Journal of Developmental Biology

Int. J. Dev. Biol. 66: 391 - 400 (2022)

Vol 66, Issue 7-8-9

Single-cell transcriptomics defines Dot1L interacting partners and downstream target genes in the mouse molar dental pulp

Original Article | Published: 21 February 2023

Rosa Guzzo1, Badam Enkhmandakh2, Timothy Becker3, Pujan Joshi4, Paul Robson5, Anushree Vijaykumar6, Mina Mina6, Dong-Guk Shin4, Dashzeveg Bayarsaihan2,7,*

1Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA, 2Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA, 3Computing Sciences Department, University of Hartford, West Hartford, CT, USA, 4Computer Science and Engineering Department, University of Connecticut, Storrs, CT, USA, 5The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA, 6Department of Craniofacial Sciences, University of Connecticut Health Center, Farmington, CT, USA, 7Institute for System Genomics, University of Connecticut, Storrs, CT, USA


Although histone methyltransferases are implicated in many key developmental processes, the contribution of individual chromatin modifiers in dental tissues is not well understood. Using single-cell RNA sequencing, we examined the expression profiles of the disruptor of telomeric silencing 1-like (Dot1L) gene in the postnatal day 5 mouse molar dental pulp. Dot1L is the only known enzyme that methylates histone 3 on lysine 79, a modification associated with gene expression. Our research revealed 15 distinct clusters representing different populations of mesenchymal stromal cells (MSCs), immune cells, pericytes, ameloblasts and endothelial cells. We documented heterogeneity in gene expression across different subpopulations of MSCs, a good indicator that these stromal progenitors undergo different phases of osteogenic differentiation. Interestingly, although Dot1L was broadly expressed across all cell clusters within the molar dental pulp, our analyses indicated specific enrichment of Dot1L within two clusters of MSCs, as well as cell clusters characterized as ameloblasts and endothelial cells. Moreover, we detected Dot1L co-expression with protein interactors involved in epigenetic activation such as Setd2, Sirt1, Brd4, Isw1, Bptf and Suv39h1. In addition, Dot1L was co-expressed with Eed2, Cbx3 and Dnmt1, which encode epigenetic factors associated with gene silencing and heterochromatin formation. Dot1l was co-expressed with downstream targets of the insulin growth factor and WNT signaling pathways, as well as genes involved in cell cycle progression. Collectively, our results suggest that Dot1L may play key roles in orchestrating lineage-specific gene expression during MSC differentiation.


Dot1L, histone methyltransferase, dental pulp, stem cells, H3K79me2

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