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| Status |
Public on Feb 01, 2021 |
| Title |
Hypothalamic estrogen receptor alpha mediates key side effects of tamoxifen therapy in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Adjuvant tamoxifen therapy for invasive breast cancer improves patient survival but comes with side effects that impact health and quality of life. Partly due to a lack of proven animal models, the tissues and cells that mediate these negative side effects are largely unknown. Here we show that mice undergoing a 28-day course of tamoxifen treatment experience dysregulation of core and skin temperature, changes in bone density, and decreased physical activity, recapitulating several aspects of the human response. Single cell RNA sequencing reveals that tamoxifen induces widespread gene expression changes in the hypothalamus, particularly in neurons and ependymal cells. These effects are largely dependent on estrogen receptor alpha (ERα), as conditional ERα knockout ablated or reversed tamoxifen-induced changes in gene expression, thermoregulation, bone, and movement. These findings provide mechanistic insights into the effects of tamoxifen on the hypothalamus and suggest that hypothalamic ERα mediates several side effects of tamoxifen therapy.
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| Overall design |
A total of sixteen hypothalami were analyzed. Group sizes are as follows: Wild-type, control injections n = 3; Wild-type, tamoxifen injections n = 5; Esr1cKO, control injections n = 4, Esr1cKO tamoxifen injections n = 4
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| Contributor(s) |
Zhang Z, Park JW, Ahn IS, Diamante G, Sivakumar N, Arneson DV, Yang X, van Veen JE, Correa SM |
| Citation(s) |
33647234 |
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| Submission date |
Oct 02, 2020 |
| Last update date |
Mar 11, 2021 |
| Contact name |
John Edward van Veen |
| E-mail(s) |
jevanveen@gmail.com
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| Organization name |
UCLA
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| Department |
Integrative Biology and Physiology
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| Lab |
van Veen
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| Street address |
610 Charles E young Dr
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA667095 |
| SRA |
SRP286217 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158960_RAW.tar |
150.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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