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1、Cell (JL) phase contrast. (A) Normal HeLa cells; (B) treated with staurosporin to induce apoptosis; or (C) treated with thapsigargin to induce autophagy (Galluzzi et al, 2007). (D) Apoptotic, and (E) necroptotic Jurkat cells (Degterev et al, 2005). (F) Paraptotic 293T cells (Sperandio et al, 2000; c
2、opyright (2000) National Academy of Sciences, USA). (G) Necrotic and (H) autophagic iBMK cells (Degenhardt et al, 2006; Mathew et al, 2007). (I) Ras-expressing U251 glioblastoma cells showing macropinosomes (J.H. Overmeyer, A. Kaul, E.E. Johnson (3) 經(jīng)轉(zhuǎn)基因的克隆哺乳動(dòng)物,將能為人類提供源源不斷的廉價(jià)的藥品、保健品以及較易被人體接受的移植器官; (
3、4) 科學(xué)家將很快地從目前的同種克隆技術(shù)推進(jìn)到異種克隆,即借腹懷胎的新領(lǐng)域,這無疑將大大促進(jìn)對瀕臨滅種的哺乳動(dòng)物的保護(hù)工作。,克隆技術(shù)將對21世紀(jì)產(chǎn)生的重大影響(?),56,PPT學(xué)習(xí)交流,第一節(jié) 細(xì)胞的特征 細(xì)胞的基礎(chǔ)知識 細(xì)胞的生長、分化與死亡 第二節(jié) 動(dòng)物細(xì)胞工程 動(dòng)物細(xì)胞培養(yǎng) 單克隆抗體 動(dòng)物克隆 干細(xì)胞工程,57,PPT學(xué)習(xí)交流,Stem cells are powerful tools in biology and medicine. What can scientists do with these cells to exploit their incredible potent
4、ial?,Adapted fromPrinciples of Biologypublished byNature Education.,JAMES KING-HOLMES/SCIENCE PHOTO LIBRARY A mouse embryo is held in place during nuclear transfer. The eggs genetic material has been removed and an adult cell nucleus is injected in its place.,四. 干細(xì)胞工程,58,PPT學(xué)習(xí)交流,Pluripotent: can tra
5、nsform into any one of the 220 cell types in the human body. Self-renewal: one stem cell can also divide to produce millions more stem cells.,1. What are Stem Cells?,59,PPT學(xué)習(xí)交流,in nearly all animals, from tiny worms to mice and humans. embryonic stem cells adult stem cells induced pluripotent stem (
6、iPS) cells,2. Types of Stem Cells,60,PPT學(xué)習(xí)交流,Embyonic Stem Cells VS. Adult Stem Cells,Stem Cells: Flexible friends Nature483,S22S26,61,PPT學(xué)習(xí)交流,In the past decade, scientists have also learned to make stem cells from regular mature, differentiated cells. These cells are called induced pluripotent ste
7、m cells because scientists force them to become pluripotent even after they have reached a differentiated state. By turning up the expression of just a few genes, scientists can force a skin cell, for example, to retrace its developmental pathway backwards all the way to a flexible pluripotent state
8、.,Induced Pluripotent Stem Cells,62,PPT學(xué)習(xí)交流,3. Medical Applications,Stem cells can teach us about the biology of pluripotent cells, how the human body develops, and what happens during disease. They are also a tool for developing safer ways to design and test new medications. they are the basis for
9、regenerative medicine, using stem cells to repair damaged tissue. ,63,PPT學(xué)習(xí)交流,The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modificati
10、ons are not irreversible. We have obtained a new view of the development of cells and organisms. Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to
11、remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells. For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells consti
12、tute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.,From surprising discovery to medical use,皮膚細(xì)胞,iPS,神經(jīng)細(xì)胞,心肌細(xì)胞,肝細(xì)胞,精子、卵子,64,PPT學(xué)習(xí)交流,Why is a therapeutic cloning approach important?,By growing new body parts from existing ones fro
13、m the same person we can avoid transplant rejection problems. By using cells re-engineered or “cloned” from ourselves we can become our own transplant source - similar to banking blood for ourselves before a surgical operation.,65,PPT學(xué)習(xí)交流,People in the US affected by diseases that may be helped by s
14、tem cell research,ConditionNumber of Persons Affected Cardiovascular diseases 58 Million Autoimmune diseases 30 Million Diabetes16 Million Osteoporosis10 Million Cancer8.2 Million Alzheimers disease4 Million Parkinsons disease1.5 Million Burns (severe) 0.3 Million Spinal cord injuries0.25 Million Bi
15、rth defects150,000 (per year) Total 128.4 Million - Data from the Patients Coalition for Urgent Research, Washington, DC (according to Perry, Ref. 267).,66,PPT學(xué)習(xí)交流,NATURE|NEWS Chinas stem-cell rules go unheeded Health ministrys attempt at regulation has had little effect. Nature484,149150(12 April 2
16、012),Its boom time for firms selling stem-cell treatments, such as those derived from umbilical blood. LIU HAIFENG/XINHUA PRESS/CORBIS,67,PPT學(xué)習(xí)交流,NATURE|NEWS Stem-cell therapy takes off in Texas A boom in unproven procedures is worrying scientists. Nature483,1314(01 March 2012),Celltex hosts the lar
17、gest stem-cell bank in the United States. TYLER RUDICK,68,PPT學(xué)習(xí)交流,4. Development of the Stem Cell technique,Source:,69,PPT學(xué)習(xí)交流,Where are the Stem Cells?,自然胚胎 克隆人胚胎-核移植/混種胚胎-核移植 體細(xì)胞誘導(dǎo)多能干細(xì)胞 (體細(xì)胞轉(zhuǎn)分化),70,PPT學(xué)習(xí)交流,In 1868, German biologist Ernst Haeckel first used the term stem cell to describe a zygote.
18、Researchers have been working with mouse embryonic stem cells since 1981. the field took off in 1998, when researchers isolated human embryonic stem cells for the first time. (最早的人類多能干細(xì)胞是從體外受精的臨床病例中得來的多余胚泡。這個(gè)里程碑式的事件是James Thomson領(lǐng)導(dǎo)的University of Wisconsin, Madison的實(shí)驗(yàn)室在1998年的成果。 ),3.1 Isolation and c
19、ulture of Stem Cells,71,PPT學(xué)習(xí)交流,3.2 Objections to Stem Cell Reasearch,72,PPT學(xué)習(xí)交流,2008紐卡斯?fàn)柎髮W(xué)將從人類皮膚細(xì)胞中提取的DNA注入來自母牛卵巢的卵子,卵子的所有遺傳物質(zhì)基本上都被去除。,3.3 Interspecies Embryos,2003上海第二醫(yī)科大學(xué)盛慧珍教授研究組將人的體細(xì)胞核植入去核的兔卵細(xì)胞中。,73,PPT學(xué)習(xí)交流,3.4 Adult Stem Cells,do not raise the ethical questions that embryonic stem cells do beca
20、use no embryos are needed exist in very small numbers often buried deep in the tissue mainly used for two treatments: bone-marrow transplants to rebuild a patients immune system, and skin grafts to replace skin over a burn or other injury other applications for adult stem cells?use drugs to activate
21、 a patients own adult stem cells to perform the necessary repairs?,74,PPT學(xué)習(xí)交流,For a long time, scientists thought that once a cell differentiated, it could never regain its pluripotency. They assumed that it must be set in its identity because it had so many genes turned on and off in ways particula
22、r to that cell type. In 2006, however, Kazutoshi Takahashi and Shinya Yamanaka of Kyoto University in Japan proved otherwise. They turned mouse skin cells specifically, fibroblasts into stem cells. These were the first induced pluripotent stem (iPS) cells.,3.5 Induced Pluripotent Stem Cells,75,PPT學(xué)習(xí)
23、交流,The first direct reprogramming of adult human fibroblasts. Ian Wilmut Scottish Centre for Regenerative Medicine, University of Edinburgh In 2007 issues of Cell and Science, Yamanaka and colleagues (Takahashi et al., 2007) and Yu and colleagues (Yu et al., 2007) demonstrate that expression of four
24、 specific transcription factors gives adult human fibroblasts many of the characteristics of human embryonic stem cells. Refinements of this procedure will make it possible to produce pluripotent human cell lines without use of an embryo. There are profound scientific and social implications of this
25、 research.,Cell Stem Cell, 2007 Dec 13;1(6):593-4.,I decided a few weeks ago not to pursue nuclear transfer - the method used to create Dolly the sheep, he said, admitting the new method was easier to accept socially.,76,PPT學(xué)習(xí)交流,十年科學(xué)進(jìn)展 1. The Dark Genome:基因組中的“暗物質(zhì)” 3. Ancient DNA:古生物的DNA 5. Reprogra
26、mming Cells:細(xì)胞重編程 6. The Microbiome:人體內(nèi)微生物組 8. Inflammation:炎癥反應(yīng)的陰暗面,Science, Dec. 2010,77,PPT學(xué)習(xí)交流,The Nobel Prize in Physiology or Medicine 2012. N. 21 Feb 2013,The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body.
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