PXD026681 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | NGLY1 deficiency perturbs cerebral development by affecting stress tolerability and neural stem cell signaling during neurogenesis |
Description | Although NGLY1 deficiency has been discovered as a result of mutations in the NGLY1 gene, cellular and molecular mechanisms underlying the neurological abnormalities due to NGLY1 malfunction in the brain remain mostly unknown. Using human cerebral organoid (CO) models and systems biology techniques, we uncovered NGLY1 deficiencyinduced alterations at the early stage of cerebral development. Despite the similar vitality and cellular pluripotency of NGLY1-functional and -deficient WA09 hESCs, COs developed from the NGLY1-deficient hESCs had the defective formation of SATB2+ upper-layer neurons and attenuation of STAT3 and HES1 signaling critical for sustaining radial glia. The NGLY1-deficient CO cells, compared with the NGLY1-functional ones, also presented higher vulnerability to multiple stressors. Bulk and single-cell analysis of transcriptomes revealed that NGLY1-deficient COs showed a propensity for premature neuronal differentiation, accompanied by significant downregulation of secretory and transcription factors, including TTR, IGFBP2, and ID4. Supplementing recombinant TTR to NGLY1-deficient CO cells reduced their susceptibility to proteasome inhibition. Ectopic expression of NGLY1 led to IGFBP2 and ID4 upregulation in CO cells developed from NGLY-deficient patientderived induced pluripotent stem cells (iPSCs). Moreover, ID4 expression, STAT3 signaling, and proliferation were enhanced by treatment of recombinant IGFBP2 in CO cells developed from the NGLY1-deficient WA09 hESCs and patient-derived iPSCs. Our findings indicate that NGLY1 could be critical for regulating various stress responses and maintaining neural stem cells (NSCs) in the developing cerebrum. In patients, NGLY1 deficiencyassociated neurological abnormalities, including microcephaly, may be a consequence of aberrations in NSC signaling sustained by NGLY1. |
HostingRepository | PRIDE |
AnnounceDate | 2022-05-20 |
AnnouncementXML | Submission_2022-05-20_02:47:37.959.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Parul Mittal |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-14 05:35:03 | ID requested | |
⏵ 1 | 2022-05-20 02:47:38 | announced | |
Publication List
Lin VJT, Hu J, Zolekar A, Salick MR, Mittal P, Bird JT, Hoffmann P, Kaykas A, Byrum SD, Wang YC, Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids. Cell Death Dis, 13(3):262(2022) [pubmed] |
Keyword List
submitter keyword: NGLY1, congenital deglycosylation disorder, neurodevelopment, neuroprogenitors, human pluripotent stem cells, cerebral organoids, stress responses, secretory factors |
Contact List
Prof Dr. Peter Hoffmann |
contact affiliation | Strand Leader BENM, Lloyd Sansom Chair Future Industries Institute, UniSA |
contact email | Peter.Hoffmann@unisa.edu.au |
lab head | |
Parul Mittal |
contact affiliation | Research associate |
contact email | pearl106@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026681
- Label: PRIDE project
- Name: NGLY1 deficiency perturbs cerebral development by affecting stress tolerability and neural stem cell signaling during neurogenesis