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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70304
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dc.contributor.advisor林頌然(Sung-Jan Lin)
dc.contributor.authorYao-Wen Hsuen
dc.contributor.author許耀文zh_TW
dc.date.accessioned2021-06-17T04:25:33Z-
dc.date.available2020-08-16
dc.date.copyright2018-08-16
dc.date.issued2018
dc.date.submitted2018-08-14
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Kobielak, K., Pasolli, H.A., Alonso, L., Polak, L., and Fuchs, E. (2003). Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA. J Cell Biol 163, 609-623.
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Li, J.L., Goh, C.C., Keeble, J.L., Qin, J.S., Roediger, B., Jain, R., Wang, Y., Chew, W.K., Weninger, W., and Ng, L.G. (2012). Intravital multiphoton imaging of immune responses in the mouse ear skin. Nat Protoc 7, 221-234.
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Mesa, K.R., Rompolas, P., Zito, G., Myung, P., Sun, T.Y., Brown, S., Gonzalez, D.G., Blagoev, K.B., Haberman, A.M., and Greco, V. (2015). Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature 522, 94-97.
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Sugaya, K., Ishihara, Y., Inoue, S., and Hirobe, T. (2015). The effects of gamma rays on the regeneration of hair follicles are carried over to later hair cycles. Int J Radiat Biol 91, 957-963.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70304-
dc.description.abstract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。zh_TW
dc.description.abstractThe 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.en
dc.description.provenanceMade available in DSpace on 2021-06-17T04:25:33Z (GMT). No. of bitstreams: 1
ntu-107-R05548048-1.pdf: 3237740 bytes, checksum: 12e72bf06682b6156a2fdca00477c71f (MD5)
Previous issue date: 2018
en
dc.description.tableofcontents口試委員審定書 i
致謝 ii
中文摘要 iii
Abstract iv
Introduction 1
The structure of hair follicle 1
The morphogenesis and cycle of hair follicle 5
Ionizing radiation 9
Hair follicle dystrophy model 10
Two-photon microscopy 14
Specific aim 14
Material and methods 15
Mice 15
Synchronization of the hair follicle cycle 15
Radiation exposure 16
UVB exposure 16
Immunofluorescence staining 16
TUNEL assay 17
Intravital imaging 18
Transmission electron microscopy (TEM) 19
Image Processing 20
Results 21
HFs entry from telogen to anagen in day 11 after depilation 21
Matrix cells mitosis in the homeostasis anagen during the early phase 25
Matrix cell deaths in IR-injured anagen during the early phase 27
Engulfment of apoptotic cells in HF matrix 30
Sunburn cells in UVB-injured skin 30
Cells do not have significant movement in the homeostasis anagen during the late phase 33
ORS cells migrate downward and proliferate in lower tip position during the late phase after radiation injury 35
Discussion 41
Hair growth after depilation on the dorsal ear skin of mice 41
Apoptosis in the matrix and the removal of the apoptotic cells 42
Downward migration of basal ORS cells 43
References 45
dc.language.isoen
dc.subject游離輻射zh_TW
dc.subject毛囊zh_TW
dc.subject再生zh_TW
dc.subject細胞遷移zh_TW
dc.subject細胞凋亡zh_TW
dc.subject吞噬作用zh_TW
dc.subjectEngulfmenten
dc.subjectHair follicleen
dc.subjectIonizing radiationen
dc.subjectRegenerationen
dc.subjectApoptosisen
dc.subjectMigrationen
dc.title游離輻射造成的毛囊再生:不同部位的動態協調zh_TW
dc.titleHair follicle regeneration after ionizing radiation: the dynamic coordination of distinct compartmentsen
dc.typeThesis
dc.date.schoolyear106-2
dc.description.degree碩士
dc.contributor.oralexamcommittee楊宗霖(Tsung-Lin Yang),郭青齡(Chin-Lin Guo)
dc.subject.keyword毛囊,游離輻射,再生,細胞凋亡,吞噬作用,細胞遷移,zh_TW
dc.subject.keywordHair follicle,Ionizing radiation,Regeneration,Apoptosis,Engulfment,Migration,en
dc.relation.page48
dc.identifier.doi10.6342/NTU201803381
dc.rights.note有償授權
dc.date.accepted2018-08-15
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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