(发育生物学)VIII-干细胞生物学课件.ppt

1、(发育生物学）VIII 干细胞生物学More than 200 clearly recognizable differentiated cell types in mammalsThe fertilized eggs in development undergo successive cell differentiation,forming a variety of different cell lineagesHypodermis:皮下组织皮下组织,Coelomocyte:体腔细胞体腔细胞Stem cells can be identified during the successive d

2、ifferentiation of different cell lineages in developmentConcept of stem cells in the context of developmentn Stem cells are defined as a cell population that has the capacity both to self-renew and to give rise to at least one kind of nondividing,fully differentiated descendant.n Stem cells can be i

3、dentified during the successive differentiation of different cell lineages in development,thus,are classified based on their developmental potential,developmental stages etcThe stem cell classificationdevelopmental potentialn Totipotent（全能干细胞）（全能干细胞）:Ability of a single cell to divide and produce al

4、l the differentiated cells in an organism,including extraembryonic tissues-Examples:the fertilized egg,blastomeres of early morulasn Pluripotent（多潜能干细胞）（多潜能干细胞）:Potential of a cell to generate all cell types except extraembryonic tissue-Examples:embryonic stem cells and induced pluripotent stem(ips)

5、cellsn Multipotent（多能干细胞）（多能干细胞）:Potential of a cell to form several lineages within a tissue-Examples:Haematopoietic stem cells n Unipotent（单能干细胞）（单能干细胞）:Potential of a cell to form a single lineage within a tissue-Examples:Epidermal stem cellsThe stem cell classificationdevelopmental stagesn Early

6、 Development Embryonic stem cells(ESc)Germline stem cells(GSC)Induced pluripotent stem cells(iPSCs)n The germ layer derived developmentEctodermNeural stem cellsEpidermal stem cellsMesodermHematopoietic stem cellsMesenchymal stem cellsEndoderm Liver stem cellsPancreatic stem cellsStem cells in the ep

7、ithelium of the small intestine and colonStem cell biology 1 Introduction2 Early Development2.1 Embryonic stem cells(ESc)2.2 induced pluripotent stem cells(iPSCs)2.3 Germline stem cells(GSC)3 The germ layer derived development 3.1 Ectoderm3.1.1 Neural stem cells3.1.2 Epidermal stem cells3.2 Mesoderm

8、3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cellsStem cell biology 3.3 Endoderm 3.3.1 Liver stem cells3.3.2 Pancreatic stem cells3.3.3 Stem cells in the epithelium of the small intestine and colonStem cell biology(I)1 Introduction2 Early Development2.1 Embryonic stem cells(ESc)2.2 induced p

9、luripotent stem cells(iPSCs)2.3 Germline stem cells(GSC)3 The germ layer derived development 3.1 Ectoderm3.1.1 Neural stem cells3.1.2 Epidermal stem cells3.2 Mesoderm3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cellsEmbryonic stem cells(ESc)in mammalsES cells are pluripotent stem cells deriv

10、ed from the inner cell mass(ICM)of fertilized eggs in mammals.Both mouse and human ES cells have a virtually unlimited self-renewing capacity and are theoretically able to give rise to all cells(more than 200)in the body,including functional germ cellsMouse ES cell lines in 1981,Martin Evans and Mat

11、thew KaufmannHuman ES cell lines in 1998,James ThomsonThe biological properties of mouse ES cells The importance of ES cells in biology and medicinen Exploring the regulatory mechanisms underlying cell differentiation,both genetic and epigeneticn Gene targeting gene function studiesmouse model of hu

12、man diseasesn Regenerative medicine/Cell-replacement therapyThe Nobel Laureates in Physiology or Medicine 2007For their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells-gene targeting Dr Mario CapecchiDr Martin EvansDr Oliver SmithiesTh

13、e importance of ES cells in biology and medicinen Exploring the regulatory mechanisms underlying cell differentiation,both genetic and epigeneticn Gene targeting gene function studiesmouse model of human diseasesn Regenerative medicine/Cell-replacement therapy(an alternative to conventional organ tr

14、ansplantation)degenerative brain disorders(Alzheimer or Parkinson disease)or spinal cord injuriesdiabetesanemiasimmune deficiencies+LIF(cytokine leukemia inhibitory factor)+Different combinations of growth factors Culture of human ES cells on mouse bone marrow produces hematopoietic stem cells(HSCs)

15、which could further differentiate into numerous types of blood cellsCThe drawback of ES cells in medical applicationsn Immune rejectionTherapeutic cloning(somatic nuclear transplantation)Induced pluripotent stem cells(iPSc)n Tumor formationEnsure that only a pure population of differentiated ES cell

16、s is used for the cell/tissue transplantationn The ethical problemiPS cellsAdult stem cellsStem cell biology(I)1 Introduction2 Early Development2.1 Embryonic stem cells(ESc)2.2 induced pluripotent stem cells(iPSCs)2.3 Germline stem cells(GSC)3 The germ layer derived development 3.1 Ectoderm3.1.1 Neu

17、ral stem cells3.1.2 Epidermal stem cells3.2 Mesoderm3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cellsInduced pluripotent stem cells(iPSCs)Generation of iPS cells refers to the reprogramming of a somatic cell into a cell with pluripotency.The idea is related to the somatic cell reprogramming

18、 or somatic cell cloning dated back to 50 years ago in Xenopus studies in which the cloned embryos were derived from injection of somatic cell nucleus into an enucleated oocyte.iPS cells generated from both mouse embryonic and adult fibroblast cells in 2006,Shinya Yamanaka(山中伸弥山中伸弥)Human iPS cells i

19、n 2007,Shinya YamanakaThe Nobel Laureates in Physiology or Medicine 2012John GurdonShinya YamanakaFor their discovery that mature cells can be converted to stem cellsiPS cell derived mouse and its F1 progeniesThe importance of iPS cells in biology and medicinen Probe mammalian development and epigenetic reprogramming n Replacement of human ES cells for therapeutic purpose Minimize the likehood of immune rejectionTechnically quick and efficientAvoid ethical concerns:no oocyte requirement and destruction of embryosn Drug target discovery SMA:spinal muscular atrophy