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| Status |
Public on Sep 06, 2022 |
| Title |
Vitamin C Potentiates Plasma Cell Differentiation via TET-mediated DNA modification [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Ascorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genomewide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients can cooperate with epigenetic enzymes to regulate gene expression. Our finding also implies that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
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| Overall design |
The characterize the effect of vitamin C on the transcritomes in B cells.
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| Contributor(s) |
Lio J, Chen H, Almonte-Loya A |
| Citation(s) |
36069787 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K22 CA241290 |
TET-mediated Epigenetic Regulation in the Development and Immunoevasion of B cell Lymphoma |
OHIO STATE UNIVERSITY |
Chan-Wang Jerry Lio |
|
| BioProject |
PRJNA759658 |
| |
| Submission date |
Sep 08, 2021 |
| Last update date |
Dec 06, 2022 |
| Contact name |
Chan-Wang Jerry Lio |
| E-mail(s) |
lio.4@osu.edu
|
| Organization name |
Ohio State University
|
| Street address |
460 W 12th Ave
|
| City |
Columbus |
| State/province |
Ohio |
| ZIP/Postal code |
43210 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE183681 |
Epigenetic Remodeling by Vitamin C Potentiates Plasma Cell Differentiation |
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