SAMN46479249
External Id
The Second Affiliated Hospital of Shantou University Medical College
INSDC center name
2025-02-06T00:50:21.680Z
INSDC first public
2025-02-06T00:50:21.680Z
INSDC last update
live
INSDC status
Human
NCBI submission model
Human.1.0
NCBI submission package
missing
age
missing
biomaterial_provider
human embryonic palatal mesenchymal cell
cell_line
2024-01-01
collection_date
Tobacco smoke (TS), a major indoor air pollutant, poses a significant health threat, notably increasing the incidence of congenital malformations, particularly cleft palate (CP). Despite our incomplete understanding of the mechanisms by which TS induces CP, this study offers profound insights through the integration of multi-omics with Mendelian Randomization (MR) analysis. By utilizing two-sample MR and sensitivity analyses, we identified causal metabolites associated with CP, including pathogenic (ursodeoxycholate, 10-undecenoate (11:1n1), gamma-glutamylphenylalanine) and protective (glycerate, glycochenodeoxycholate, isobutyrylcarnitine) metabolites. Further metabolomic profiling of human embryonic palatal mesenchymal (HEPM) cells exposed to cigarette smoke extract (CSE) revealed that downregulated 3-phosphoglycerate (3-PG) is vital in glycine, serine, and threonine metabolism and the pentose phosphate pathway, both of which are linked to CP-protective metabolites. This underscores the importance of the downregulation of CP-protective metabolites and their metabolic disruptions in TS-induced CP. To investigate protein-level changes regulating 3-PG metabolism, we conducted correlation analysis and functional enrichment using proteomics data, revealing that lysosomal function, extracellular matrix-receptor interaction, and carbon compound metabolism associated with TS-induced CP. To complement these findings, we performed cellular localization and domain enrichment analyses on proteins involved in these functions. Gene Set Variation Analysis of transcriptome sequencing data identified significant downregulation of platelet-derived growth factor binding and glycosaminoglycan (GAG) degradation, which are closely related to the protein functions involved in 3-PG metabolism. Through integrated transcriptome-MR analysis, we discovered CP-related genes (TMTC1, CYP1B1, IL32) that are downregulated by CSE and positively associated with GAG degradation. Notably, TMTC1 emerged as a protective gene for CP, further suggesting that TS-induced CP may be related to the reduction of protective factors. In conclusion, this groundbreaking multi-omics study, combined with MR analysis, not only uncovers biomarkers and key dysfunction related to TS-induced CP but also provides new perspectives and theoretical support for future research in this field.
description
China
geo_loc_name
human embryonic palatal mesenchymal cell
isolate
Homo sapiens
http://purl.obolibrary.org/obo/NCBITaxon_9606
organism
not collected
sex
palate
tissue
Identification of Potential Key Targets and Mechanisms Underlying Cleft Palate Induced by Tobacco Smoke Exposure through Multi-omics Integrated Mendelian Randomization Analysiss
title