Summary of project PR001773
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
| 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 |
Summary of all studies in project PR001773
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002831 | Folate depletion upregulates heme synthesis | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 8 | Uploaded data (578.9M)* |
| ST002892 | Folate levels in K562 cells following folate depletion | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 23 | Uploaded data (1.1G)* |
| ST002893 | Folate depletion time-course in MEL cells with analysis for porphyrin metabolites | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 21 | Uploaded data (1.1G)* |
| ST002894 | Folate levels in MEL cells following folate depletion | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 22 | Uploaded data (1.3G)* |
| ST002895 | Polar metabolite levels in K562 cells following folate depletion and inosine supplementation | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (1.1G)* |
| ST002896 | Polar metabolite levels in MEL cells following folate depletion and inosine supplementation | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (1.1G)* |
| ST002897 | Polar metabolite levels in K562 cells following folate depletion, SHIN1 or AICAR treatment | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (1.3G)* |
| ST002898 | Polar metabolite levels in MEL cells following folate depletion, SHIN1 or AICAR treatment | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (1.3G)* |
| ST002899 | Polar metabolite levels in erythroid progenitor cells following SHIN1 and inosine treatment | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (1.4G)* |
| ST002900 | Folate metabolite levels in erythroid progenitor cells following SHIN1 and inosine treatment | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 12 | Uploaded data (600.6M)* |
| ST002905 | Porphyrin analysis of K562 cells following C13-Serine and C13-Glycine tracing during folate depletion. | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 24 | Uploaded data (3.8G)* |
| ST002906 | Polar metabolite levels in K562 cells following short-term folate depletion | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 15 | Uploaded data (1.7G)* |
| ST002907 | Folate levels in K562 cells following short-term folate depletion | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 15 | Uploaded data (0.9G)* |
| ST002912 | Polar metabolite levels in MEL cells following folate depletion | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 22 | Uploaded data (2.4G)* |
| ST002913 | Polar metabolite levels in K562 cells following folate depletion | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 23 | Uploaded data (2.1G)* |
| ST002990 | Folate depletion time-course in K562 cells with analysis for porphyrin metabolites | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 20 | Uploaded data (1.5G)* |
| ST002992 | Polar metabolite levels in K562 cells following C13-Serine and C13-Glycine tracing | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 24 | Uploaded data (2.8G)* |
| ST003018 | Polar metabolite levels in K562 cells following PKC inhibition in 2,000 nM or 100 nM FA conditions | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 16 | Uploaded data (1.9G)* |
| ST003020 | Polar metabolite levels in MEL cells following PKC inhibition in 2,000 nM or 100 nM FA conditions | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 16 | Uploaded data (2G)* |
| ST003021 | Porphyrin metabolite levels in K562 cells following PKC inhibition in 2,000 nM or 100 nM FA conditions | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 16 | Uploaded data (1.1G)* |
| ST003022 | Porphyrin metabolite levels in MEL cells following PKC inhibition in 2,000 nM or 100 nM FA conditions | Mus musculus | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 16 | Uploaded data (859.8M)* |
| ST003023 | Porphyrin metabolite levels in K562 cells following 6 day culture in 2,000 nM or 100 nM folic acid | Homo sapiens | Boston Children's Hospital, Harvard Medical School | MS | 2024-02-13 | 1 | 8 | Uploaded data (445.5M)* |
