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细胞分化与基因表达调控

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细胞分化与基因表达调控nullCell differentiation and Cancer cells Cell differentiation and Cancer cells Cell differentiationChapter 121. About the concept of cell differentiationThe process that a cell changes to carry out a specialized function: Marked by: Morphology / Structure / F...

细胞分化与基因表达调控
nullCell differentiation and Cancer cells Cell differentiation and Cancer cells Cell differentiationChapter 121. About the concept of cell differentiationThe process that a cell changes to carry out a specialized function: Marked by: Morphology / Structure / FunctionnullThe different cell types of a multicellular organism contain the same DNA. A cell can change the expression of its genes in response to external signals. Differences in mRNA expression patterns among different cell types. Different cell types synthesize different sets of proteins. Gene expression can be regulated at many of the steps in the pathway from DNA to RNA to protein.nullThe four essential processes by which a multicellular organism is made: Cell proliferation, Cell specialization, Cell interaction, and Cell movement.nullCell differentiation occurs in multicellular organismsHuman: 1014 cells, >200 cell typesnull2. Why a fertilized egg can develop into different cells: Gene differentiated express 分子杂交技术检测基因及其表达null3. Combinational control and Gene differentiated express pp.416: 12-1: 2n (n=3, A,B,C)null4. House-keeping genes and luxury genesHouse-keeping genes: Expressed in all cell types, essential for all cellsLuxury genes: Tissue-specific genes, expressed in special cellsSequential expression of various genes in early Drosophila embryonull5. Transdifferentiation: From one type of cell into another typeIncludes: Dedifferentiation---Redifferentiation去分化再分化Cell totipotency (细胞全能性)Cell totipotency (细胞全能性)1. Plant cellsThe ability of a cell develops into a complete organism 植物细胞具有全能性,在适宜条件下可培育成完整植株,已广泛应用null2. Animal cloning—Transplantation of frog red cell nucleus indicated the nucleus of animal is totipotency(全能性)A new organism created by the process of nuclear transplantationnullDolly: A lamb with no father cThe sheep star: Dollynull克隆能给人类带来什么?克隆动物是未来的制药厂克隆的爱因斯坦会懂“相对论”吗Stem cell and its differentiation potentialStem cell and its differentiation potential 1. What is a stem cell ?Has two abilities: (1)Self-renewing (2)Differentiatingnull2. Where to get the stem cells?(1) Embryonic stem cells null(2) Adult stem cellsnull(3) Umbilical cord blood stem cells (4) Fetal stem cells null3. Types of stem cells: differentiation potential(1) Monopotential stem cellnull(2) Pluripotent stem cellsnullnull(3) Embryonic stem cellsnullTwo ways for a stem cell to produce daughters with different fatesnull4.Why do researchers study stem cells ?For repairing tissue damage caused by disease or injury, including: Diseases that impair brain function, such as Alzheimer's disease and Parkinson's disease Spinal cord injuries Blood diseases, including leukemias Burns null5. Stem cell plasticityAdult stem cells can differentiate into a large number of different cell types. Turning blood into brain: Science, 2000, 290: 1779-1782Turning brain into blood: Science, 1999, 283: 534-535NSC+EGF & FGF: Growing See also: Current opinion in cell biology, 13: 662-665, 2001nullProduction of differentiated cells from mouse ES cells in culture.nullStem cells migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration.利用干细胞可塑性nullRegeneration of new tissues from our own cells will not be far behind Science, December 6, 2002: 1901Cancer: Cells proliferate uncontrollablyCancer: Cells proliferate uncontrollablyTumorBenign tumors: Do not spreadMalignant tumors — Cancers: MetastasizenullBenign tumorMalignant tumornull1. The biology characteristics of cancer(1) Cell proliferate uncontrollably(2) Invade and metastasizenull(3) Less well differentiated than normal cells or benign tumor cells(4) Have highly aberrant chromosome complements— AneuploidyPancreas cancernull(5) Lose Contact inhibition in vitro null2. The causes of cancerCarcinogenic chemicals and UVDNA and RNA tumor viruses Alter the genomeSV40, Adenovirus HIVBenign tumorMalignant tumorNormal cellnull3. Caner: As a result of the accumulation of mutation and natural selectionCancer-inducing mutation genesProto-oncogenesTumor-suppressor genesnull癌基因(oncogenes):v-onc and c-onc 抑癌基因(tumor-suppressor gene)Rb p53 特 点 原癌基因 抑癌基因 基因属性 细胞增殖必需 细胞分化必需 致癌方式 基因突变激活、异常表达 基因缺失或失活 Rous(1910)发现鸡的致癌RNA病毒; 1963年发现RSV突变株: tsRSV 鸡成纤维细胞 40C37C细胞正常 病毒正常繁殖细胞癌变 病毒正常繁殖tdRSV 鸡成纤维细胞40C37C细胞正常 细胞正常 病毒正常繁殖病毒正常繁殖 v-oncogenetdRSV3’端缺失1500-2000bp; 不影响病毒复制,但影响细胞转化null1976年发现,正常鸡细胞核DNA中,具有与V-onc的同源序列,称正常细胞中的同源序列为原癌基因(protooncogene),或C-oncogene. v-onc和c-onc的关系:c-onc来自v-onc. 理由如下: 1、v-onc对病毒复制和生存都是不必要的;而c-onc对细胞重要功能和活动不可缺少;提示c-onc是进化中保存下来的细胞重要结构元件。 2、发现的30种c-onc是依靠病毒的v-onc探针找到的;并不是所有c-onc都有对应的同源v-onc。 3、v-src缺失3/4不能致癌的RSV,注入鸡体内,发现缺失的v-src与c-src发生重组,v-src回复并致癌。抑癌基因(tumor suppressor gene) Harris(1968):癌细胞系与同组织正常细胞融合杂交细胞无恶性表型,也不致癌; 随着染色体丢失则可能恢复致癌(Rb—13q14.1).nullProto-oncogenes null(1) Proto-oncogens: Gain-of-function mutationsRas oncogene: Retain bind GTPBcl-2 oncogene: Prevent apoptosisnull(2) Tumor suppressor genes: Loss-of-function mutations nullRb gene: The first tumor suppressor gene in patient with retinoblastomanullp53: Guardian of the genomeBecause the accumulation of gene mutation and Natural selection, so the patient is agednullChart of the major signaling pathways relevant to cancer in human cells, indicating the cellular locations of some of the proteins modified by mutation in cancers.nullCan we treat cancer?1. Conventional approaches to combating cancerSurgery Chemotherapy/RadiationCan not rid of all cancer cellsnull2. Gene therapyTumor cells lack functional tumor-suppressor genesp53-bearing virusesEngineered adenovirusImmune responsenull3. Inhibiting the formation of blood vesselsAngiogenesis: Cancer cells — growth factors — endothelial cells — form new vesselsnullDr. Folkman’s War: Angiogenesis and the struggle to defeat cancernull "Remember, you are only an expert from things done in the past. There are no experts from things that will happen in the future." Dr. Folkman
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