Summary of Study ST002893
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 PR001773. The data can be accessed directly via it's Project DOI: 10.21228/M8J420 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.
| Study ID | ST002893 |
| Study Title | Folate depletion time-course in MEL cells with analysis for porphyrin metabolites |
| Study Summary | Culture of MEL cells in RPMI media containing 100 nM folic acid for 0, 1, 2, 4, 6, or 8 days followed my LC-MS targeting porphyrin metabolites. This is a reverse timecourse where all samples are harvested on the same day. Day 0 in 100 nM folic acid indicates 8 days culture in 2,000 nM folic acid. |
| Institute | Boston Children's Hospital, Harvard Medical School |
| Department | pathology |
| Laboratory | Kanarek Lab |
| Last Name | Kanarek |
| First Name | Naama |
| Address | Enders 1116.2, 300 Longwood Ave, Boston, MA 02115 |
| naama.kanarek@childrens.harvard.edu | |
| Phone | 6173557433 |
| Submit Date | 2023-09-28 |
| Num Groups | 5 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-13 |
| Release Version | 1 |
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Project:
| Project ID: | PR001773 |
| Project DOI: | doi: 10.21228/M8J420 |
| Project Title: | Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis |
| Project Summary: | Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines, and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, AICAR, followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation. This is phenocopied by inhibition of folate metabolism using the SHMT1/2 inhibitor - SHIN1, and by AICAR supplementation. Mechanistically, the metabolically-driven differentiation is independent of nucleotide sensing through mTORC1 and AMPK, and is instead mediated by protein kinase C (PKC). Our findings suggest that folate deprivation-induced premature differentiation of erythroid progenitor cells is a molecular etiology to folate-deficiency induced anemia. |
| Institute: | Boston Children's Hospital, Harvard Medical School |
| Department: | pathology |
| Laboratory: | Kanarek Lab |
| Last Name: | Kanarek |
| First Name: | Naama |
| Address: | Enders 1116.2, 300 Longwood Ave, Boston, MA 02115 |
| Email: | naama.kanarek@childrens.harvard.edu |
| Phone: | (617) 355-7433 |
