Summary of project PR001752
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 PR001752. The data can be accessed directly via it's Project DOI: 10.21228/M87Q7Z This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001752 |
| Project DOI: | doi: 10.21228/M87Q7Z |
| Project Title: | IL-1β-mediated adaptive re-programming of endogenous human cardiac fibroblasts to cells with immune features during fibrotic remodeling |
| Project Summary: | The source and roles of fibroblasts and CD4 helper T-cells during maladaptive remodeling and myocardial fibrosis in pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a sub-population of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial/perivascular lesions of SUGEN/Hypoxia (SuHx) rats and fibroblasts labelled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68 positive cell clusters. IL-1β also activates stemness markers such as NANOG and SOX2 and genes involved in de-differentiation, lymphoid cell function and metabolic reprogramming. IL-1β induction of lineage traced primary mouse cardiac fibroblasts causes these cells to lose their fibroblast identity and acquire an immune phenotype. Our results identify IL-1β induced immune-competency in human cardiac fibroblasts and suggest that fibroblast secretome modulation may constitute a therapeutic approach to PAH and other diseases typified by inflammation and fibrotic remodeling. |
| Institute: | Brown University |
| Department: | MPPB |
| Laboratory: | Siamwala Lab |
| Last Name: | Siamwala |
| First Name: | Jamila |
| Address: | 830 Chalkstone Avenue, Building 35 |
| Email: | jamila_siamwala@brown.edu |
| Phone: | 6192136223 |
Summary of all studies in project PR001752
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002805 | IL-1β-mediated adaptive re-programming of endogenous human cardiac fibroblasts to cells with immune features during fibrotic remodeling | Homo sapiens | Brown University | MS | 2023-08-07 | 1 | 6 | Uploaded data (559.5K)* |
