PXD032075-1

PXD032075 is an original dataset announced via ProteomeXchange.

Title	A CRISPR-engineered Isogenic Model Reveals Altered Neuronal Phenotypes of the 22q11.2 A-B Syndromic Deletion
Description	The 22q11.2 deletion syndrome (22q11.2DS) is the most common copy number variant (CNV)-associated syndrome, leading to congenital and neuropsychiatric anomalies. Patient-derived, induced pluripotent stem cell (iPS) models have provided important insight into the mechanisms of phenotypic features of this condition. However, patient-derived iPSC models may harbor underlying genetic heterogeneity that can confound analysis of pathogenic CNV effects. Furthermore, the ~1.5 Mb “A-B” deletion at this locus is inherited at higher frequency than the more common ~2.7 Mb “A-D” deletion, but remains under-studied due to lack of relevant models. To address these issues, here we leveraged a CRISPR-based strategy in Cas9-expressing iPS cells to engineer novel isogenic models of the 22q11.2 “A-B” deletion. After in vitro differentiation to excitatory neurons, integrated transcriptomic and cell surface proteomics identified deletion-associated alterations in surface adhesion markers. Furthermore, implantation of iPS-derived neuronal progenitor cells into the cortex of neonatal mice found decreased proliferation and accelerated neuronal maturation within a relevant microenvironment. Taken together, our results suggest potential pathogenic mechanisms of the 22q11.2 “A-B” deletion in driving neuronal and neurodevelopmental phenotypes. We further propose that the isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.
HostingRepository	PRIDE
AnnounceDate	2023-05-11
AnnouncementXML	Submission_2023-05-11_08:57:57.799.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu-HsiuLin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-05 05:24:09	ID requested
⏵ 1	2023-05-11 08:57:58	announced

Dataset with its publication pending

submitter keyword: Isogenic, neurons, proteomics, CNV,iPSC, 22q11.2DS, CRISPR, xenotransplant

Arun P.Wiita
contact affiliation	Department of Laboratory Medicine, Wiita Lab, University of California, San Francisco, USA
contact email	arun.wiita@ucsf.edu
lab head
Yu-HsiuLin
contact affiliation	University of California, San Francisco
contact email	lin.yu.hsiu@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032075
     1. Label: PRIDE project
     2. Name: A CRISPR-engineered Isogenic Model Reveals Altered Neuronal Phenotypes of the 22q11.2 A-B Syndromic Deletion