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Series GSE192700 Query DataSets for GSE192700
Status Public on Dec 28, 2022
Title Aberrant Nrf2 activation delays erythroid maturation during chemotherapeutic drug-induced erythropoiesis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Nuclear factor (erythroid-derived 2)-like2 (Nrf2) and miR-144/451 regulate two well-established systems that have been identified to maintain redox homeostasis in erythroid cells by removing excess reactive oxygen species (ROS). Whether Nrf2 plays a role in the differentiation process during erythropoiesis has not been reported. In this study, we demonstrate that miR-144/451 gene knockout (KO) in mice dampens erythroid differentiation when 5-Fluorouridine is used to induce acute anemia. Surprisingly, inactivation of Nrf2 by crossing Nrf2 KO mice completely alleviates the delayed erythropoiesis in miR-144/451 KO mice. Nrf2 is a miR-144/451 target and depletion of miR-144/451 leads to the derepression of Nrf2, and thus an overexpression of Nrf2. Therefore, our findings indicate that persistent Nrf2 activation blocks erythroid maturation. We further reveal that even physiological levels of Nrf2 impair the erythroid differentiation. The underlying mechanism is that hyperactivity of Nrf2 leads to the sustained proliferation of erythroblasts partially by activation of Myc signaling. We also find that Nrf2 and miR-144/451 coordinate to scavenge ROS but do not phenotypically copy each other, indicating that they control two distinct anti-oxidant systems in erythroid cells. Furthermore, we find that miR-144/451 deficiency produces a more profound defect of erythropoiesis than dysfunctional Nrf2. Given that Nrf2 is ubiquitously expressed in tumor tissues, which facilitates cancer malignancy and chemoresistance; and that cancer is often accompanied by anemia that markedly inhibits antineoplastic treatment efficacy and anticancer immunity, our findings suggest that targeting Nrf2 holds great promise that not only harms cancer cells, but also reverses cancer-related anemia.
 
Overall design mRNAs from four groups of mouse erythroblasts derived from spleens 11 days after 5-FU treatment
 
Contributor(s) Yang L, Yu D
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Submission date Dec 28, 2021
Last update date Dec 30, 2022
Contact name Lei Yang
E-mail(s) young210716@sina.com
Phone +8618752788543
Organization name Yangzhou University Medical College
Street address 136 Jiangyang Road
City Yangzhou
State/province Jiangsu
ZIP/Postal code 225009
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM5761263 erythroblasts, WT-1
GSM5761264 erythroblasts, WT-3
GSM5761265 erythroblasts, m-1
Relations
BioProject PRJNA792789

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE192700_RAW.tar 2.1 Mb (http)(custom) TAR (of TXT)
GSE192700_total_count.txt.gz 513.8 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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