Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells

Li, Chunhong1; Yu Shangguan2,3; Zhu, Peng2; Dai, Weier4; Tang, Donge2; Ou, Minglin1; Dai, Yong2

2021-10-27

10.1186/s41065-021-00204-x

HEREDITAS   影响因子和分区

1601-5223

Background Autosomal dominant osteopetrosis type II (ADO2) is a genetically and phenotypically metabolic bone disease, caused by osteoclast abnormalities. The pathways dysregulated in ADO2 could lead to the defects in osteoclast formation and function. However, the mechanism remains elusive. Materials and methods To systematically explore the molecular characterization of ADO2, we performed a multi-omics profiling from the autosomal dominant osteopetrosis type II iPSCs (ADO2-iPSCs) and healthy normal control iPSCs (NC-iPSCs) using whole genome re-sequencing, DNA methylation and N6-methyladenosine (m6A) analysis in this study. Results Totally, we detected 7,095,817 single nucleotide polymorphisms (SNPs) and 1,179,573 insertion and deletions (InDels), 1,001,943 differentially methylated regions (DMRs) and 2984 differential m6A peaks, and the comprehensive multi-omics profile was generated from the two cells. Interestingly, the ISG15 m6A level in ADO2-iPSCs is higher than NC-iPSCs by IGV software, and the differentially expressed m6A-modified genes (DEMGs) were highly enriched in the osteoclast differentiation and p53 signaling pathway, which associated with the development of osteopetrosis. In addition, combining our previously published transcriptome and proteome datasets, we found that the change in DNA methylation levels correlates inversely with some gene expression levels. Conclusion Our results indicate that the global multi-omics landscape not only provides a high-quality data resource but also reveals a dynamic pattern of gene expression, and found that the pathogenesis of ADO2 may begin early in life.

Osteopetrosis Osteoclast Whole genome sequencing DNA methylation N6-methyladenosine

SCI

英语

通讯

Science and Technology Planning Project of Guangdong Province, China[2017B020209001] ; National Natural Science Foundation of China[82060393] ; National Science Foundation for Young Scientists of China[31700795] ; science and technology plan of Shenzhen[JCYJ20180305163846927] ; Guangxi Natural Science Foundation[2020GXNSFAA159124]

Genetics & Heredity

Genetics & Heredity

WOS:000711417300001

BMC

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Guilin Med Univ, Affiliated Hosp 2, Guangxi Hlth Commiss Key Lab Glucose & Lipid Meta, Cent Lab, Guilin 541199, Guangxi, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Jinan Univ,Clin Med Coll 2,Shen, Clin Med Res Ctr,Guangdong Prov Engn Res Ctr Auto, Shenzhen 518020, Guangdong, Peoples R China
3.924 Hosp, Cent Lab Guilin, Guangxi Key Lab Metab Dis Res, Guilin 541002, Peoples R China
4.Univ Texas Austin, Coll Nat Sci, Austin, TX 78712 USA

Li, Chunhong,Yu Shangguan,Zhu, Peng,et al. Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells[J]. HEREDITAS,2021,158(1).

Li, Chunhong.,Yu Shangguan.,Zhu, Peng.,Dai, Weier.,Tang, Donge.,...&Dai, Yong.(2021).Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells.HEREDITAS,158(1).

Li, Chunhong,et al."Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells".HEREDITAS 158.1(2021).