碩士 / 國立臺灣海洋大學 / 生物科技研究所 / 102 / Hypoxia-inducible factor (HIF) is a hypoxia-responsive transcriptional factor which could upregulate a number of downstream genes, including erythropoiesis, angiogenesis, and anti-apoptosis, to protect cells against hypoxic impairs. In human erythrocyte progenitor cells, hypoxia increases erythrocyte production and enhances Gata1 transcription by HIF1α activity. Overexpression of Hif1α increased Gata1 expression, while depletion of Hif1α decreased Gata1 expression in K562 cells and inhibited erythrocyte production. It was shown that GATA1 plays critical roles in erythrocyte differentiation and maturation. Although HIF1α plays critical function in hypoxia-induced erythropoiesis, it is unclear whether HIF1α also mediates the process of primitive erythrocyte production s during development. Previously, it was shown that hif1α depletion inhibited a number of erythroid-specific genes and decreased erythrocyte production. Here I demonstrated that hif1α depletion resulted in decrease of gata1 expression and inhibition of primitive erythrocyte production. Likewise, gata1 knockdown also inhibited erythroid-specific genes and abrogated primitive erythrocyte differentiation. Ectopic gata1 cRNA could partially rescue expression of erythrocyte-specific genes and erythrocyte production in hif1α morphant, indicating that HIF1α mediates the process of primitive erythrocyte differentiation through the action of its downstream gata1 expression. Our results indicates that HIF1α not only involves in hypoxia-induced erythropoiesis, it also mediates embryonic erythrocyte differentiation in normoxia environment.
| Identifer | oai:union.ndltd.org:TW/102NTOU5613011 |
| Date | January 2014 |
| Creators | Lin, Yi-Xuan, 林怡萱 |
| Contributors | Hu, Chin Hwa, 胡清華 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 33 |
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