Summary of project PR001272
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 PR001272. The data can be accessed directly via it's Project DOI: 10.21228/M89402 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001272 |
| Project DOI: | doi: 10.21228/M89402 |
| Project Title: | Metabolic profiles of murine stress erythroid progenitors |
| Project Summary: | Inflammation alters hematopoiesis, skewing production to generate myeloid effector cells at the expense of steady state erythropoiesis. To compensate, stress erythropoiesis is induced to maintain homeostasis until the inflammation is resolved. Unlike the constant production of steady state erythropoiesis, stress erythropoiesis generates a bolus of new erythrocytes by first producing immature progenitor cells, which then transition to committed erythroid progenitors and differentiate. We hypothesize that the proliferation of early progenitor cells and their transition to differentiation is regulated by changes in metabolism. Metabolomics and isotope tracing analysis was performed to assess the intracellular metabolic profiles in proliferating progenitors isolated from in vitro stress erythropoiesis cultures. We observed an active engagement of glucose metabolism in glycolysis and anabolic biosynthesis, while the levels of TCA intermediates suggested that TCA cycle and mitochondrial respiration were blocked. Concomitantly, inducible nitric oxide synthase (iNOS) was induced in progenitor cells to increase the production of nitric oxide (NO), which was demonstrated to be crucial for proliferating progenitor metabolism. Inhibition or genetic mutation of iNOS decreased NO levels resulting in the suppression of progenitor proliferation in vitro and in vivo. As evaluated by RNA-seq, inhibition of iNOS suppressed cell proliferation-related pathways including cell cycle and nucleotide metabolism, while upregulating erythroid differentiation genes. These data suggest that iNOS-derived NO production establishes a metabolism that promotes the proliferation of progenitor cells while inhibiting their differentiation. In contrast, the transition to differentiation is marked by decreased Nos2 expression and a change in metabolism to support induction of the erythroid gene expression program. These data support a model where increased pro-inflammatory signals inhibit steady state erythropoiesis, while at the same time promoting stress erythropoiesis to maintain homeostasis. |
| Institute: | Pennsylvania State University |
| Department: | Veterinary and Biomedical Sciences |
| Laboratory: | Paulson Lab |
| Last Name: | Paulson |
| First Name: | Robert |
| Address: | 228 AVBS Building, Shortlidge Road, University Park, PA 16802 |
| Email: | rfp5@psu.edu |
| Phone: | 814-863-6306 |
Summary of all studies in project PR001272
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002007 | Isotope tracing analysis of stress erythroid progenitors | Mus musculus | Pennsylvania State University | MS | 2022-12-12 | 1 | 25 | Uploaded data (12.5G)* |
| ST002009 | Metabolomics analysis of stress erythroid progenitors | Mus musculus | Pennsylvania State University | MS | 2022-03-11 | 1 | 15 | Uploaded data (4.3G)* |
| ST002499 | Metabolomics analysis of stress erythroid progenitors (Part 2) | Mus musculus | Pennsylvania State University | MS | 2023-03-22 | 1 | 20 | Uploaded data (12G)* |
