PXD014227-1

PXD014227 is an original dataset announced via ProteomeXchange.

Title	Genotyping, generation and lysine 2-hydroxyisobutyrylation identification of the first human autosomal dominant osteopetrosis type II specific induced pluripotent stem cells
Description	Background: Autosomal dominant osteopetrosis type II (ADO2) is a rare human genetic disease that has been broadly studied as an important osteopetrosis model; however, there are no disease-specific induced pluripotent stem cells (ADO2-iPSCs) that may be valuable for understanding the pathogenesis and may be a potential source of cells for autologous cell therapy. Methods: To generate the first human ADO2-iPSCs from a Chinese family with ADO2 and to identify their characteristics, blood samples were collected from the proband and his parents and were used for genotyping by whole-exome sequencing (WES); the urine-derived cells of the proband were reprogrammed with episomal plasmids that contained transcription factors, such as KLF4, OCT4, c-MYC, and SOX2. The proteome-wide analysis of lysine 2-hydroxyisobutyrylation in the ADO2-iPSCs and control cell lines was performed by high-resolution LC-MS/MS and a bioinformatics analysis. Results: WES with filtering strategies identified a mutation in CLCN7 (R286W) in the proband and his father, which was absent in the proband’s mother and the healthy controls; this was confirmed by Sanger sequencing. The ADO2-iPSCs were successfully generated, which carried the normal male karyotype (46, XY) and carried the mutation of CLCN7 (R286W); the ADO2-iPSCs positively expressed alkaline phosphatase and other surface markers; and no vector and transgene was detected. The ADO2-iPSCs could differentiate into all three germ cell layers, both in vitro and in vivo. Our proteomic profiling detected 7, 405 proteins and revealed 3,684 2-hydroxyisobutyrylated sites in 1,036 proteins in the ADO2-iPSCs. Conclusions: Our data indicated that mutation CLCN7 (R286W) may be a cause of the osteopetrosis family. The generated vector-free and transgene-free ADO2-iPSCs with identified lysine 2-hydroxyisobutyrylation may be valuable for personalized and cell-based regenerative medicine in the future.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:02:30.793.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Donge Tang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-12 02:46:57	ID requested
⏵ 1	2022-02-15 09:02:31	announced

Li C, Shangguan Y, Zhu P, Dai W, Tang D, Ou M, Dai Y, Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells. Hereditas, 158(1):40(2021) [pubmed]

submitter keyword: osteopetrosis, whole exome sequencing, CLCN7, iPSCs, 2-hydroxyisobutyrylation

Yong Dai
contact affiliation	Clinical Medical Research Center of Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, No.1017, Dongmen North Road, Luohu District, Shenzhen 518020, China.
contact email	daiyong22@aliyun.com
lab head
Donge Tang
contact affiliation	Shenzhen People’s Hospital
contact email	donge66@126.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD014227

PRIDE project URI

• PRIDE
  1. PXD014227
     1. Label: PRIDE project
     2. Name: Genotyping, generation and lysine 2-hydroxyisobutyrylation identification of the first human autosomal dominant osteopetrosis type II specific induced pluripotent stem cells