AI Article Synopsis
- - The FoxO3 transcription factor plays a crucial role in managing oxidative stress and the maturation of blood cells during their development (erythropoiesis), especially in the context of β-thalassemia, a blood disorder.
- - In this study, researchers created a lab model using blood stem cells from β-thalassemia patients and discovered that FoxO3 activity significantly drops during the final stages of blood cell development, unlike in healthy cells where it remains active.
- - The decreased FoxO3 activity in β-thalassemia also leads to lower levels of its target genes and increased AKT phosphorylation, suggesting that targeting the PI3K/AKT pathway might be a promising treatment approach for this condition.
Article Abstract
The FoxO3 transcription factor is a key regulator of oxidative stress and erythroid maturation during erythropoiesis. In this study, we explored the involvement of FoxO3 in severe β-thalassemia. Using primary CD34+ hematopoietic progenitor cells from patients with β-thalassemia major, we successfully developed an in vitro model of ineffective erythropoiesis. Based on this model, FoxO3 activity was quantified in single cells using high throughput imaging flow cytometry. This study revealed a significant reduction of FoxO3 activity during the late stage of erythroblast differentiation in β-thalassemia, in contrast to erythropoiesis in normal cells that maintain persistent activation of FoxO3. In agreement with the decreased FoxO3 activity in β-thalassemia, the expression of FoxO3 target genes was also found to decrease, concurrent with elevated phosphorylation of AKT, most clearly at the late stage of erythroid differentiation. Our findings provide further evidence for the involvement of FoxO3 during terminal erythropoiesis and confirm the modulation of the PI3K/AKT pathway as a potential therapeutic strategy for β-thalassemia.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669432 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187610 | PLOS |
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