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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48720

Title: HIF1 alpha-GATA1控制斑馬魚胚胎原始紅血球發育
Primitive Erythropoiesis is mediated by HIF1 alpha-GATA1 Axis in Zebrafish Embryo
Authors: Lin, Yi-Xuan
林怡萱
Contributors: 國立臺灣海洋大學:生命科學暨生物科技學系
Keywords: HIF1α低氧誘發因子;斑馬魚;初期紅血球生成;GATA1轉錄因子
HIF1;zebrafish;primitive erythropoiesis;GATA1
Date: 2014
Issue Date: 2018-08-22T06:30:42Z
Abstract: 低氧對細胞構成壓力,此時Hypoxia-inducible factor (HIF)為低氧時一個重要的轉錄因子,能啟動下游基因來降低缺氧的損害,如紅血球生成、血管增生等等。先前的研究指出在低氧環境下,人類慢性髓系細胞以及具有紅血球分化能力的CD34+造血幹細胞中,HIF1α能直接調控human的GATA1,增加HIF1α的表現可增強GATA1的表現,而弱化HIF1α則使GATA1的表現下降,並且使紅血球表面maker CD71及CD235a的表現減少。近年來許多研究也指出GATA1參與紅血球的生成,它調控著紅血球細胞的分化及成熟。本研究主要在探討斑馬魚Hif1是否是藉由調控gata1的表現,進而調控其他血球相關基因而影響了紅血球的生成。過去的研究發現抑制hif1α會降低血球相關基因的表現,進而抑制紅血球的生成。本研究發現弱化hif1α後會減弱胚胎內gata1的表現,而弱化gata1後亦可觀察到類似hif1α弱化後的情況,減少血球相關基因的表現,並且幾乎觀察不到紅血球的生成。此外,在hif1α弱化的胚胎內,以外加的方式注射入gata1 cRNA可以回復胚胎內血球相關基因的表現,顯示在hif1α弱化所造成的紅血球生成受到抑制與gata1的表現減少有關。本實驗的結果顯示在胚胎內初期紅血球的生成過程中,HIF1α扮演了非常重要的功能,透過對gata1基因的控制,影響紅血球細胞的分化過程。這項研究也推斷在脊椎動物中缺氧環境所誘發紅血球的生成,其中有部分的原因是由HIF1α增加Gata1的表現,進而促進紅血球的生成。
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.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010136013.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/48720
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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