<scp>DNA</scp> methylation profile of lip tissue from congenital nonsyndromic cleft lip and palate patients by whole‐genome bisulfite sequencing

Zhang, Bowen; Zhang, Youmeng; Wu, Siyi; Ma, Ding; Ma, Jing

doi:10.1002/bdr2.2102

Cited by 3 publications

(1 citation statement)

References 54 publications

(64 reference statements)

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“…All RNA-seq data used in this study was accessed from NCBI (SRR13662566). SRA were selected for samples related to CL/P and six patient sample SRAs were downloaded as uploaded by Zhang et al 22 . This set contains whole blood samples from 4 CL/P patients and 2 healthy controls.…”

Section: Methodsmentioning

confidence: 99%

Mucin-7 as a Potential Candidate Risk Allele for Cleft Lip and/or Palate

Montel,

Rengifo,

Chang

2024

Preprint

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Cleft lip and/or palate (CL/P) occur in approximately 1 in 700 live births in the United States. High hereditary rates (50-80%) of CL/P indicate a strong genetic cause. The concept of strong genetic causes has been well-demonstrated in previous studies such as GWAS studies that identified IRF6 for Van der Woode syndrome. Since the risk for genetic factors is strongly associated with CL/P, we hypothesized that RNA sequencing (RNA-seq) from CL/P patients may reveal enriched genes. Differential expression analysis examined changes in gene expression in CL/P patients compared to healthy controls, and gene-enrichment in relevant pathways. To explore the relationship between variants driving the observed changes in gene expression, we performed variant analysis and reported all CL/P-specific single nucleotide polymorphisms (SNPs). Our findings demonstrate that the normally upregulated MUC7 gene is significantly downregulated in CL/P patients. Using our list of prioritized differentially expressed genes (DEGs), we observed significantly enriched pathways for biological processes related to cornification, skin and epidermis development, and keratinocyte and epidermal cell differentiation. By performing variant analyses, a single nucleotide polymorphism (SNP) in MUC7, and 47 SNPs in 20 additional genes (CLCA4, ETNK2, ERLNC1, HAL, HOPX, IVL, KLK11, LIPK, LY6D, MUC21, NCCRP1, NEBL, PHYH, SERPINB11, SERPINB4, SORD, SPINK5, SULT2B1, TMEM154, TMPRSS11A) were revealed. To our knowledge, this is the first report on the potential role of MUC7 in contributing to CL/P. Together, these findings provide further insight into the genetic causes of CL/P.

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Section: Methodsmentioning

confidence: 99%

Mucin-7 as a Potential Candidate Risk Allele for Cleft Lip and/or Palate

Montel,

Rengifo,

Chang

2024

Preprint

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DNA methylation profile of lip tissue from congenital nonsyndromic cleft lip and palate patients by whole‐genome bisulfite sequencing

Zhang

et al. 2022

Birth Defects Research

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Congenital nonsyndromic cleft lip and palate (NSCLP) is one of the most common malformations worldwide. DNA methylation has been implicated in many diseases. However, its involvement in lip tissue from NSCLP is not well understood. This study aimed to investigate the role of dysregulated DNA methylation in NSCLP. DNA methylation profile was determined in eight injured and five self-normal lip tissue samples from children with NSCLP by whole-genome bisulfite sequencing. A total of 2,711 differentially methylated regions (DMRs), corresponding to 1,231 genes were identified. Given the important role of promoter methylation in regulating gene expression, the promoter DMR-related genes were considered. Bioinformatics analysis demonstrated that some of them showed potential associations with NSCLP.Therefore, the well-known NSCLP susceptibility gene, GLI family zinc finger 2 (GLI2) with an unknown role in its DNA methylation in NSCLP, was selected for further analysis. The promoter hypomethylation and higher mRNA expression level of GLI2 were observed in injured lip tissues by verification in additional samples. Moreover, dual luciferase reporter assay indicated that promoter hypermethylation of GLI2 inhibited its transcription. Overall, this study suggested that abnormal DNA methylation in lip tissue may be correlated with the pathogenesis of congenital NSCLP.

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Single-cell Transcriptome Landscape of DNA Methylome Regulators Associated with Orofacial Clefts in the Mouse Dental Pulp

Enkhmandakh

Joshi

Robson

et al. 2023

The Cleft Palate Craniofacial Journal

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Objective Significant evidence links epigenetic processes governing the dynamics of DNA methylation and demethylation to an increased risk of syndromic and nonsyndromic cleft lip and/or cleft palate (CL/P). Previously, we characterized mesenchymal stem/stromal cells (MSCs) at different stages of osteogenic differentiation in the mouse incisor dental pulp. The main objective of this research was to characterize the transcriptional landscape of regulatory genes associated with DNA methylation and demethylation at a single-cell resolution. Design We used single-cell RNA sequencing (scRNA-seq) data to characterize transcriptome in individual subpopulations of MSCs in the mouse incisor dental pulp. Settings The biomedical research institution. Patients/Participants This study did not include patients. Interventions This study collected and analyzed data on the single-cell RNA expssion in the mouse incisor dental pulp. Main outcome measure(s) Molecular regulators of DNA methylation/demethylation exhibit differential transcriptional landscape in different subpopulations of osteogenic progenitor cells. Results scRNA-seq analysis revealed that genes encoding DNA methylation and demethylation enzymes (DNA methyltransferases and members of the ten-eleven translocation family of methylcytosine dioxygenases), methyl-DNA binding domain proteins, as well as transcription factors and chromatin remodeling proteins that cooperate with DNA methylation machinery are differentially expressed within distinct subpopulations of MSCs that undergo different stages of osteogenic differentiation. Conclusions These findings suggest some mechanistic insights into a potential link between epigenetic alterations and multifactorial causes of CL/P phenotypes.

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DNA methylation profile of lip tissue from congenital nonsyndromic cleft lip and palate patients by whole‐genome bisulfite sequencing

Cited by 3 publications

References 54 publications

Mucin-7 as a Potential Candidate Risk Allele for Cleft Lip and/or Palate

Mucin-7 as a Potential Candidate Risk Allele for Cleft Lip and/or Palate

DNA methylation profile of lip tissue from congenital nonsyndromic cleft lip and palate patients by whole‐genome bisulfite sequencing

Single-cell Transcriptome Landscape of DNA Methylome Regulators Associated with Orofacial Clefts in the Mouse Dental Pulp

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