(发育生物学)VIII干细胞生物学.ppt

(发育生物学）VIII 干细胞生物学,More than 200 clearly recognizable differentiated cell types in mammals,The fertilized eggs in development undergo successive cell differentiation,forming a variety of different cell lineages,Hypodermis:皮下组织,Coelomocyte:体腔细胞,Stem cells can be identified during the successive differentiation of different cell lineages in development,Concept of stem cells in the context of development,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.Stem cells can be identified during the successive differentiation of different cell lineages in development,thus,are classified based on their developmental potential,developmental stages etc,The stem cell classificationdevelopmental potential,Totipotent（全能干细胞）:Ability of a single cell to divide and produce all the differentiated cells in an organism,including extraembryonic tissues-Examples:the fertilized egg,blastomeres of early morulas Pluripotent（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)cells Multipotent（多能干细胞）:Potential of a cell to form several lineages within a tissue-Examples:Haematopoietic stem cells Unipotent（单能干细胞）:Potential of a cell to form a single lineage within a tissue-Examples:Epidermal stem cells,The stem cell classificationdevelopmental stages,Early Development Embryonic stem cells(ESc)Germline stem cells(GSC)Induced pluripotent stem cells(iPSCs)The germ layer derived developmentEctodermNeural stem cellsEpidermal stem cellsMesodermHematopoietic stem cellsMesenchymal stem cellsEndoderm Liver stem cellsPancreatic stem cellsStem cells in the epithelium of the small intestine and colon,Stem 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 Mesoderm3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cells,Stem 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 colon,Stem 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 Neural stem cells3.1.2 Epidermal stem cells3.2 Mesoderm3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cells,Embryonic stem cells(ESc)in mammals,ES cells are pluripotent stem cells derived 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 Matthew KaufmannHuman ES cell lines in 1998,James Thomson,The biological properties of mouse ES cells,The importance of ES cells in biology and medicine,Exploring the regulatory mechanisms underlying cell differentiation,both genetic and epigenetic Gene targeting gene function studiesmouse model of human diseases Regenerative medicine/Cell-replacement therapy,The Nobel Laureates in Physiology or Medicine 2007,For their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells-gene targeting,Dr Mario Capecchi,Dr Martin Evans,Dr Oliver Smithies,The importance of ES cells in biology and medicine,Exploring the regulatory mechanisms underlying cell differentiation,both genetic and epigenetic Gene targeting gene function studiesmouse model of human diseases Regenerative medicine/Cell-replacement therapy(an alternative to conventional organ transplantation)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)which could further differentiate into numerous types of blood cells,C,The drawback of ES cells in medical applications,Immune rejectionTherapeutic cloning(somatic nuclear transplantation)Induced pluripotent stem cells(iPSc)Tumor formationEnsure that only a pure population of differentiated ES cells is used for the cell/tissue transplantation The ethical problemiPS cellsAdult stem cells,Stem 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 Neural stem cells3.1.2 Epidermal stem cells3.2 Mesoderm3.2.1 Hematopoietic stem cells3.2.2 Mesenchymal stem cells,Induced 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 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)Human iPS cells in 2007,Shinya Yamanaka,The Nobel Laureates in Physiology or Medicine 2012,John Gurdon,Shinya Yamanaka,For their discovery that mature cells can be converted to stem cells,iPS cell derived mouse and its F1 progenies,The importance of iPS cells in biology and medicine,Probe mammalian development and epigenetic reprogramming 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 embryos Drug target discovery,SMA:spinal muscular atrophy,