细胞分化与基因表达调控参考培训课件.ppt

1、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/FunctionvThe different cell types of a multicellular organism contain the same DNA.vA cell

2、 can change the expression of its genes in response to external signals.vDifferences in mRNA expression patterns among different cell types.vDifferent cell types synthesize different sets of proteins.vGene expression can be regulated at many of the steps in the pathway from DNA to RNA to protein.The

3、 four essential processes by which a multicellular organism is made:Cell proliferation,Cell specialization,Cell interaction,and Cell movement.Cell differentiation occurs in multicellular organismsHuman:1014 cells,200 cell types2.Why a fertilized egg can develop into different cells:Gene differentiat

4、ed express 细 胞 总D N A 细 胞 总RN A 输 卵 管 细 胞 成 红 细 胞 胰 岛 细 胞 输 卵 管 细 胞 成 红 细 胞 胰 岛 细 胞 卵 清 蛋 白 基 因 +-珠 蛋 白 基 因 +-+-胰 岛 素 基 因 +-+实 验 方 法 Southern杂 交 N orthern杂 交 分子杂交技术检测基因及其表达分子杂交技术检测基因及其表达3.Combinational control and Gene differentiated express pp.416:12-1:2n (n=3,A,B,C)4.House-keeping genes and luxury

5、 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 embryo5.Transdifferentiation:From one type of cell into another typeIncludes:Dedifferentiation-Rediffer

6、entiation去分化去分化再分化再分化Cell totipotency(细胞全能性细胞全能性)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2.Animal cloningTransplantation of frog red cell nucleus indicated the nucleus of animal is totipotency(全能性全能性)A new organism created by the process of

7、nuclear transplantationDolly:A lamb with no father cThe sheep star:Dolly克隆能给人类带来什么？克隆能给人类带来什么？克隆动物是未来的制药厂克隆动物是未来的制药厂克隆的爱因斯坦会懂克隆的爱因斯坦会懂“相对论相对论”吗吗Stem cell and its differentiation potential 1.What is a stem cell?Has two abilities:(1)Self-renewing(2)Differentiating2.Where to get the stem cells?(1)Embry

8、onic stem cells(2)Adult stem cells(3)Umbilical cord blood stem cells(4)Fetal stem cells 3.Types of stem cells:differentiation potential(1)Monopotential stem cell(2)Pluripotent stem cells(3)Embryonic stem cellsTwo ways for a stem cell to produce daughters with different fates4.Why do researchers stud

9、y stem cells?For repairing tissue damage caused by disease or injury,including:Diseases that impair brain function,such as Alzheimers disease and Parkinsons disease Spinal cord injuries Blood diseases,including leukemias Burns 5.Stem cell plasticityAdult stem cells can differentiate into a large num

10、ber 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,13:662-665,2001Production of differentiated cells from mouse ES cells in culture.Stem cells migrate to sites of

11、 organ damage and differentiate to cell types competent to participate in tissue regeneration.利用干细胞可塑性利用干细胞可塑性Regeneration of new tissues from our own cells will not be far behind Science,December 6,2002:1901Cancer:Cells proliferate uncontrollablyTumorBenign tumors:Do not spreadMalignant tumors Canc

12、ers:MetastasizeBenign tumorMalignant tumor1.The biology characteristics of cancer(1)Cell proliferate uncontrollably(2)Invade and metastasize(3)Less well differentiated than normal cells or benign tumor cells(4)Have highly aberrant chromosome complements AneuploidyPancreas cancer(5)Lose Contact inhib

13、ition in vitro 2.The causes of cancerCarcinogenic chemicals and UVDNA and RNA tumor viruses Alter the genomeSV40,Adenovirus HIVBenign tumorMalignant tumorNormal cell3.Caner:As a result of the accumulation of mutation and natural selectionCancer-inducing mutation genesProto-oncogenesTumor-suppressor

14、genes 癌基因（癌基因（oncogenesoncogenes）：）：v-v-onc onc and c-and c-onconc 抑癌基因（抑癌基因（tumor-suppressor genetumor-suppressor gene）Rb Rb p53p53 特特 点点 原癌基因原癌基因 抑癌基因抑癌基因 基因属性基因属性 细胞增殖必需 细胞分化必需 致癌方式致癌方式 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40C3

15、7C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15002000bp;不影响病毒复制，但影响细胞转化1976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和和c-onc的关系的关系：c-onc来自来自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

16、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（Rb13q14.1）.Proto-oncogenes(1)Proto-oncogens:Gain-of-function mutationsRas oncogene:Retain bind GTPBcl-2 oncogene:Prevent apoptosis(2)Tumor suppressor

17、genes:Loss-of-function mutations Rb gene:The first tumor suppressor gene in patient with retinoblastomap53:Guardian of the genomeBecause the accumulation of gene mutation and Natural selection,so the patient is agedChart of the major signaling pathways relevant to cancer in human cells,indicating th

18、e cellular locations of some of the proteins modified by mutation in cancers.Can we treat cancer?1.Conventional approaches to combating cancerSurgery Chemotherapy/RadiationCan not rid of all cancer cells2.Gene therapyTumor cells lack functional tumor-suppressor genesp53-bearing virusesEngineered ade

19、novirusImmune response3.Inhibiting the formation of blood vesselsAngiogenesis:Cancer cells growth factors endothelial cells form new vesselsDr.Folkmans War:Angiogenesis and the struggle to defeat cancer 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