Summary of project PR002590
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 PR002590. The data can be accessed directly via it's Project DOI: 10.21228/M8VN87 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002590 |
| Project DOI: | doi: 10.21228/M8VN87 |
| Project Title: | CREBBP-loss confers metabolic and epigenetic vulnerabilities upon lymphoma cells. |
| Project Summary: | Inactivating-mutations of CREBBP are common in diffuse large B-cell lymphoma (DLBCL). We previously demonstrated that Crebbp-/- mice develop mature B-cell malignancies preceded by a pre-malignant phase. Using single-cell RNA-seq of WT and Crebbp-/- B-cells from distinct stages of disease evolution, we discovered expansion of aberrant germinal center B-cells during disease progression. Both Crebbp-/- murine and human CRISPR-engineered isogenic CREBBP-null cells displayed reduced expression of BCR-signaling genes and increased OXPHOS transcriptional programs, a finding recapitulated in DLBCL patients with low CREBBP expression. Mechanistically, BCR-signaling decreased upon CREBBP loss, alleviating p65-mediated repression of the transcriptional coactivator PGC1β, resulting in enhanced OXPHOS transcriptional programs. This metabolic vulnerability could be targeted therapeutically. Furthermore, CREBBP-loss also conferred an epigenetic vulnerability by altering the landscape of acetylated transcription factors, including BET proteins, at super-enhancers. Combined inhibition of complex I and BET proteins exploited the metabolic and epigenetic vulnerabilities of Crebbp-/- tumors, extending lymphoma survival in vivo. |
| Institute: | Cambridge Stem Cell Institute |
| Department: | Haematology |
| Laboratory: | Huntly / Frezza |
| Last Name: | Horton |
| First Name: | Sarah |
| Address: | Puddicombe Way, Cambridge, Cambridgeshire, CB2 0AW, United Kingdom |
| Email: | sjh244@cam.ac.uk |
| Phone: | +44 1223 763368 |
Summary of all studies in project PR002590
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004120 | Assessing the dependence of murine WT and Crebbp-/- tumour B cells on glucose to fuel Oxidative Phosphorylation. | Mus musculus | Cambridge Stem Cell Institute | MS | 2025-09-01 | 1 | 11 | Uploaded data (2.1G)* |
| ST004121 | Assessing the dependence of murine WT and Crebbp-/- tumour B cells on palmitate to fuel Oxidative Phosphorylation. | Mus musculus | Cambridge Stem Cell Institute | MS | 2025-09-01 | 1 | 11 | Uploaded data (2.1G)* |
