التفاصيل البيبلوغرافية
| العنوان: |
A Synthetic Model of Human Beta-Thalassemia Erythropoiesis Using CD34+ Cells from Healthy Adult Donors. |
| المؤلفون: |
Lee, Y. Terry, Kim, Ki Soon, Byrnes, Colleen, de Vasconcellos, Jaira F., Noh, Seung-Jae, Rabel, Antoinette, Meier, Emily R., Miller, Jeffery L. |
| المصدر: |
PLoS ONE; Jul2013, Vol. 8 Issue 7, p1-7, 7p |
| مصطلحات موضوعية: |
BETA-Thalassemia, ERYTHROPOIESIS, CD34 antigen, ORGAN donors, MESSENGER RNA, APOPTOSIS, HIGH performance liquid chromatography |
| مستخلص: |
Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal phases of differentiation (culture days 14–21), beta-KD cells demonstrated increased levels of insoluble alpha-globin, as well as activated caspase-3. The majority of the beta-KD cells underwent apoptosis around the polychromatophilic stage of maturation. GDF15, a marker of ineffective erythropoiesis in humans with thalassemia, was significantly increased in the culture supernatants from the beta-KD cells. Knockdown of beta-globin expression in cultured primary human erythroblasts provides a robust ex vivo model for beta-thalassemia. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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