Summary of Study ST003108

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 PR001931. The data can be accessed directly via it's Project DOI: 10.21228/M84428 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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 IDST003108
Study TitleComplete absence of GLUT1 does not impair human terminal erythroid differentiation
Study SummaryThe Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPRmediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome.
Institute
University of Colorado
Last NameStephenson
First NameDaniel
AddressResearch 1 South L18-1303 12801 E. 17th Ave., Aurora, Colorado, 80045, USA
Emaildaniel.stephenson@cuanschutz.edu
Phone303-724-3339
Submit Date2024-02-27
Raw Data AvailableYes
Raw Data File Type(s)mzXML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-03-20
Release Version1
Daniel Stephenson Daniel Stephenson
https://dx.doi.org/10.21228/M84428
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Assay
SA333676DS1-095-007L-cultured reticulocytes 01CF19
SA333677DS1-095-014-cultured reticulocytes 01CF19
SA333678DS1-095-013-cultured reticulocytes 01CF19
SA333679DS1-095-007L+cultured reticulocytes 01CF19
SA333680DS1-095-015-cultured reticulocytes 01CF19
SA333681DS1-095-008L-cultured reticulocytes 01CF19
SA333682DS1-095-010L+cultured reticulocytes 01CF19
SA333683DS1-095-013L+cultured reticulocytes 01CF19
SA333684DS1-095-014L+cultured reticulocytes 01CF19
SA333685DS1-095-015L+cultured reticulocytes 01CF19
SA333686DS1-095-012L+cultured reticulocytes 01CF19
SA333687DS1-095-011L+cultured reticulocytes 01CF19
SA333688DS1-095-009L+cultured reticulocytes 01CF19
SA333689DS1-095-012-cultured reticulocytes 01CF19
SA333690DS1-095-008L+cultured reticulocytes 01CF19
SA333691DS1-095-009-cultured reticulocytes 01CF19
SA333692DS1-095-014L-cultured reticulocytes 01CF19
SA333693DS1-095-013L-cultured reticulocytes 01CF19
SA333694DS1-095-011-cultured reticulocytes 01CF19
SA333695DS1-095-009+cultured reticulocytes 01CF19
SA333696DS1-095-015+cultured reticulocytes 01CF19
SA333697DS1-095-014+cultured reticulocytes 01CF19
SA333698DS1-095-011+cultured reticulocytes 01CF19
SA333699DS1-095-012+cultured reticulocytes 01CF19
SA333700DS1-095-013+cultured reticulocytes 01CF19
SA333701DS1-095-008+cultured reticulocytes 01CF19
SA333702DS1-095-007+cultured reticulocytes 01CF19
SA333703DS1-095-008-cultured reticulocytes 01CF19
SA333704DS1-095-015L-cultured reticulocytes 01CF19
SA333705DS1-095-010-cultured reticulocytes 01CF19
SA333706DS1-095-007-cultured reticulocytes 01CF19
SA333707DS1-095-009L-cultured reticulocytes 01CF19
SA333708DS1-095-012L-cultured reticulocytes 01CF19
SA333709DS1-095-011L-cultured reticulocytes 01CF19
SA333710DS1-095-010L-cultured reticulocytes 01CF19
SA333711DS1-095-010+cultured reticulocytes 01CF19
SA333712DS1-095-003L-cultured reticulocytes 04CF29
SA333713DS1-095-002L-cultured reticulocytes 04CF29
SA333714DS1-095-006L-cultured reticulocytes 04CF29
SA333715DS1-095-005L-cultured reticulocytes 04CF29
SA333716DS1-095-004L-cultured reticulocytes 04CF29
SA333717DS1-095-001L+cultured reticulocytes 04CF29
SA333718DS1-095-001-cultured reticulocytes 04CF29
SA333719DS1-095-002-cultured reticulocytes 04CF29
SA333720DS1-095-003-cultured reticulocytes 04CF29
SA333721DS1-095-006+cultured reticulocytes 04CF29
SA333722DS1-095-005+cultured reticulocytes 04CF29
SA333723DS1-095-002+cultured reticulocytes 04CF29
SA333724DS1-095-003+cultured reticulocytes 04CF29
SA333725DS1-095-004+cultured reticulocytes 04CF29
SA333726DS1-095-004-cultured reticulocytes 04CF29
SA333727DS1-095-005-cultured reticulocytes 04CF29
SA333728DS1-095-004L+cultured reticulocytes 04CF29
SA333729DS1-095-005L+cultured reticulocytes 04CF29
SA333730DS1-095-006L+cultured reticulocytes 04CF29
SA333731DS1-095-003L+cultured reticulocytes 04CF29
SA333732DS1-095-002L+cultured reticulocytes 04CF29
SA333733DS1-095-006-cultured reticulocytes 04CF29
SA333734DS1-095-001+cultured reticulocytes 04CF29
SA333735DS1-095-001L-cultured reticulocytes 04CF29
SA333664DS1-095-017+Red blood cells 01CF19
SA333665DS1-095-018+Red blood cells 01CF19
SA333666DS1-095-016-Red blood cells 01CF19
SA333667DS1-095-017-Red blood cells 01CF19
SA333668DS1-095-018-Red blood cells 01CF19
SA333669DS1-095-016L+Red blood cells 01CF19
SA333670DS1-095-017L+Red blood cells 01CF19
SA333671DS1-095-017L-Red blood cells 01CF19
SA333672DS1-095-018L-Red blood cells 01CF19
SA333673DS1-095-016L-Red blood cells 01CF19
SA333674DS1-095-018L+Red blood cells 01CF19
SA333675DS1-095-016+Red blood cells 01CF19
Showing results 1 to 72 of 72
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