 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 01, 2024 |
| Title |
Hematologic DNMT3A Reduction and High Fat Diet Synergize to Promote Weight Gain and Tissue Inflammation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In the aging hematopoietic system, blood cell production becomes dominated by a limited number of hematopoietic stem cell (HSC) clones. While somatic mutations in the de novo DNA methyltransferase 3A (DNMT3A) frequently drive clone dominance, the aging milieu also likely contributes to selection of variant HSCs. The detrimental impact of clonal hematopoiesis on organismal health is thought to be mediated by differentiated progeny of variant HSCs through mechanisms as yet poorly understood. Here, we examined the interaction between high fat diet (HFD) as an inflammatory stressor and a hematopoietic system haploinsufficient for DNMT3A. Strikingly, HFD accelerated weight gain in mice harboring bone marrow with reduced DNMT3A. Moreover, distal tissues of such mice including pancreas, adipose, and spleen, harbored high levels of mutant macrophages that impacted tissue function. Aberrant DNA methylation and pro-inflammatory transcriptional activation in mutant-derived myeloid cells correlated with increased IL-6 and TNFa signaling. Together, these findings identify synergism between HFD and DNMT3A haploinsufficiency that, through increased inflammatory myeloid cell functions, can contribute to deterioration in organismal health.
|
| |
|
| Overall design |
RNA-seq performed on in vitro differentiated macrophages derived from the bone marrow of male 13-week-old DNMT3A-HET or wild-type mice.
|
| Web link |
https://www.sciencedirect.com/science/article/pii/S2589004224003432
|
| |
|
| Contributor(s) |
Reyes J, Goodell M |
| Citation(s) |
38414863 |
| |
| Submission date |
Jul 12, 2022 |
| Last update date |
Apr 01, 2024 |
| Contact name |
Margaret Goodell |
| Organization name |
Baylor College of Medicine
|
| Street address |
One Baylor Plaza, N1030
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (8)
|
| GSM6336784 |
DNMT3A-HET differentiated macrophages, IL6 treated, replicate 1, Day 8 |
| GSM6336785 |
DNMT3A-HET differentiated macrophages, Control, replicate 1, Day 8 |
| GSM6336786 |
DNMT3A-HET differentiated macrophages, IL6 treated, replicate 2, Day 8 |
| GSM6336787 |
DNMT3A-HET differentiated macrophages, Control, replicate 2, Day 8 |
| GSM6336788 |
WT differentiated macrophages, Control, replicate 1, Day 8 |
| GSM6336789 |
WT differentiated macrophages, IL6 treated, replicate 1, Day 8 |
| GSM6336790 |
WT differentiated macrophages, IL6 treated, replicate 2, Day 8 |
| GSM6336791 |
WT differentiated macrophages, Control, replicate 2, Day 8 |
|
| Relations |
| BioProject |
PRJNA858103 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE208075_counts_table.txt.gz |
4.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...