Summary of Study ST002540

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001636. The data can be accessed directly via it's Project DOI: 10.21228/M87D87 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002540
Study TitleDeriving Schwann Cells from hPSCs Enables Disease Modeling and Drug Discovery for Diabetic Peripheral Neuropathy
Study SummarySchwann cells (SCs) are the major glia of the peripheral nervous system (PNS) and are essential for its function. Defects in SCs are associated with many PNS disorders including diabetic peripheral neuropathy (DPN), a condition affecting millions of patients. We have developed a strategy for deriving SCs from human pluripotent stem cells (hPSCs) which recapitulate the molecular features of primary SCs and are capable of engrafting efficiently and producing myelin in vitro and in injured sciatic nerves in rats. We further established an hPSC-based model of DPN that revealed the selective vulnerability of human SCs to hyperglycemia-induced cytotoxicity. By high-throughput screening we found bupropion counteracts glucose-mediated cytotoxicity in SCs and normalizes glucose-induced transcriptional and metabolic abnormalities in SCs. Treatment of hyperglycemic mice with bupropion rescued sensory function, prevented SC death, and counteracted myelin damage in sciatic nerves. Our retrospective analysis of patient health records revealed that bupropion treatment was associated with a lower incidence of neuropathy among diabetic patients that receive antidepressant medications.
Institute
University of California, San Francisco
Last NameMajd
First NameHoma
Address600 16th St, Genentech Hall, S576
Emailhoma.majd@gmail.com
Phone(415) 476-6737
Submit Date2023-03-30
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2023-05-05
Release Version1
Homa Majd Homa Majd
https://dx.doi.org/10.21228/M87D87
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002646
Sampleprep Summary:Frozen total cell pellets from at least three biological repeats were submitted to the West Coast Metabolomics Center at the University of California, Davis. Agilent 7890C with Leco Pegasus HT was used for the study. Samples extracted using 1mL of 3:3:2 ACN:IPA:H2O (v/v/v). Half of the sample was dried to completeness and then derivatized using 10 uL of 40 mg/mL of Methoxyamine in pyridine. They were shaken at 30C for 1.5 hours. Then 91 uL of MSTFA + FAMEs to each sample and they were shaken at 37C for 0.5 hours to finish derivatization. Samples were then vialed, capped, and injected onto the instrument. A 7890C GC was used coupled with a LECO TOF. 0.5 uL of derivatized sample was injected using a splitless method onto a RESTEK RTX-5SIL MS column with an Intergra-Guard at 275C with a helium flow of 1 mL/min. The GC oven was set to hold at 50C for 1 min then ramped to 20C/min to 330C and then held for 5 min. The transfer line was set to 280C while the EI ion source was set to 250C. The Mass spec parameters collect data from 85m/z to 500m/z at an acquisition rate of 17 spectra/sec.
Sampleprep Protocol Filename:majd-et-al-csc-protocol.pdf
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