PXD045401
PXD045401 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Liver Steatosis and Mitochondrial Dysfunction in Spinal Muscular Atrophy is Survival Motor Neuron-Dependent and Hepatocyte-Intrinsic |
Description | Spinal Muscular Atrophy (SMA) is typically characterized as a motor neuron disease, but extra-neuronal phenotypes are present in almost every organ in severely affected patients and animal models. Extra-neuronal phenotypes were previously underappreciated as patients with severe SMA phenotypes usually died in infancy; however, with current treatments for motor neurons which increase patient lifespan, impaired function of peripheral organs may develop into significant future comorbidities and lead to new treatment-modified phenotypes. Fatty liver is seen in animal models of SMA, but generalizability to patients and whether this is due to hepatocyte-intrinsic Survival Motor Neuron (SMN) protein deficiency and/or subsequent to skeletal muscle denervation is unknown. If liver pathology in SMA is SMN-dependent and hepatocyte-intrinsic, this provides proof of concept that SMN repleting therapies must target extra-neuronal tissues as well as motor neurons for optimal patient outcome. Here we show that fatty liver is present in SMA and that SMA patient-specific iHeps are susceptible to steatosis. Using proteomics, functional studies and CRISPR/Cas9 gene editing, we confirm that fatty liver in SMA is a primary SMN-dependent hepatocyte-intrinsic liver defect associated with mitochondrial and other hepatic metabolism dysfunctions. These pathologies require monitoring and indicate the need for systematic clinical surveillance and additional and/or combinatorial therapies to ensure continued SMA patient health. |
HostingRepository | jPOST |
AnnounceDate | 2024-05-09 |
AnnouncementXML | Submission_2024-05-26_20:32:36.833.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Radoslaw Sobota |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; alpha-amino acetylated residue; deamidated L-glutamine; deamidated L-asparagine |
Instrument | instrument |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2023-09-14 20:05:20 | ID requested | |
⏵ 1 | 2024-05-26 20:32:37 | announced |
Publication List
Leow DM, Ng YK, Wang LC, Koh HW, Zhao T, Khong ZJ, Tabaglio T, Narayanan G, Giadone RM, Sobota RM, Ng SY, Teo AK, Parson SH, Rubin LL, Ong WY, Darras BT, Yeo CJ, Hepatocyte-intrinsic SMN deficiency drives metabolic dysfunction and liver steatosis in spinal muscular atrophy. J Clin Invest, 134(12):(2024) [pubmed] |
Keyword List
submitter keyword: induced hepatocellular carcinoma, spinal muscular atrophy |
Contact List
Crystal Yeo Jing Jing | |
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lab head | |
Radoslaw Sobota | |
contact affiliation | IMCB A-STAR Singapore |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
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.jpostdb.org/JPST002321/ |