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標題: | 游離輻射造成的毛囊再生:不同部位的動態協調 Hair follicle regeneration after ionizing radiation: the dynamic coordination of distinct compartments |
作者: | Yao-Wen Hsu 許耀文 |
指導教授: | 林頌然(Sung-Jan Lin) |
關鍵字: | 毛囊,游離輻射,再生,細胞凋亡,吞噬作用,細胞遷移, Hair follicle,Ionizing radiation,Regeneration,Apoptosis,Engulfment,Migration, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 毛囊是生長毛髮的皮膚器官,藉由持續循環的生長期、衰退期、休止期來調控毛髮的生長及脫落,毛囊中含有上皮細胞以及由間質細胞構成的真皮乳突,兩者的交互作用對於毛囊的再生有著重要的影響。依照游離輻射劑量的不同,生長期的毛囊對於游離輻射傷害的反應可以分為萎縮性生長期以及萎縮性衰退期,然而這兩種再生機制中的細胞動態卻仍然不明。在本研究中,我們利用穿透式電子顯微鏡、末端脫氧核苷酸轉移酶脫氧尿苷三磷酸切口末端標記技術,證明在毛囊球中,游離輻射造成的細胞凋亡會藉由被鄰近的上皮細胞吞噬達到清除的效果,利用K14-H2B-EGFP/LEF1-RFP基因轉殖小鼠以及雙光子雷射掃描顯微鏡進行活體縮時攝影,發現基底層的外根鞘細胞和lower proximal cup (LPC) 細胞會沿著基底膜進行非集體性的向下遷移,並且只有在毛囊球底部觀察到細胞有絲分裂。這些實驗結果展示了毛囊受到游離輻射傷害後的再生過程:藉由非專職吞噬作用來清除凋亡細胞、藉由基底層外根鞘細胞及LPC細胞的主動遷移來補充損失的細胞,我們認為不同細胞族群和其相異行為間的協調,造就了毛囊在游離輻射傷害後的及時再生,我們在此揭示的再生原理也可能適用於其他上皮器官。 The hair follicle (HF) is a dynamic organ that continuously cycles through anagen (growth), catagen (regression) to telogen (relative quiescence). HF is composed of epithelial cells and dermal papilla (DP) compartments and interaction between these two compartments play an important role in the regulation of HF regeneration. The responses of anagen HFs to ionizing radiation (IR) can be divided into dystrophic anagen and dystrophic catagen pathways. However, the detailed cellular dynamics of such regenerative responses of anagen HFs is still unclear. In this study, we first characterized how IR-induced apoptotic cells are removed. The results of transmission electron microscopy and TUNEL assay showed that apoptotic cells were engulfed by surviving epithelial cells in the hair bulb. Time-lapse intravital imaging in K14-H2B-EGFP/LEF1-RFP transgenic mice with two-photon microscopy showed that the basal lower proximal cup cells and basal outer root sheath cells non-collectively migrated downward toward the proximal HFs along the basement membrane. In addition, cell mitosis was only observed in lower proximal end of HFs. The results showed that the regenerative process of HFs following IR injury involved elimination of apoptotic cells by non-professional phagocytosis and active cell migration of lower proximal cup cells and basal outer root sheath cells along the basement membrane to replenish the lost cells. We propose that timely HF regeneration following IR is accomplished by coordination of different behaviors of distinct cell populations. The regenerative principle we revealed here may also be employed by other epithelial organs. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70304 |
DOI: | 10.6342/NTU201803381 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學工程學研究所 |
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