北京大学：《发育生物学 Developmental Biology》课程教学资源（PPT课件）第六章 发育中细胞分化机制

Developmental Biology 第六章发育中细胞分化机制

Developmental Biology 第六章 发育中细胞分化机制

Developmental Biology 、概念 细胞分化是指同群结构与功能相同的细胞发生一系列的内外 变化,成为结构与功能不同的细胞的过程。分化过程涉及形态 结构的变化、基因活性状态变化、细胞内物质组成的变化和功 能的变化。 细胞分化的主要特点包括: 基因表达上的变化,导致组织特异性蛋白的产生; 不同细胞在蛋白质组成上的差异导致细胞结构的不同;改 变其组成就可改变其形状,如MyoD转化; 在细胞分化的早期,不同细胞间的差异难以检测; 分化是渐进过程,进入终端分化的细胞往往不再分裂, 而终端分化后能够继续分裂的细胞可以维持和传递 终端分化状态; 细胞分化由许多细胞外信号(如细胞表面蛋白、分泌蛋白) 控制

Developmental Biology 细胞分化是指同群结构与功能相同的细胞发生一系列的内外 变化，成为结构与功能不同的细胞的过程。分化过程涉及形态 结构的变化、基因活性状态变化、细胞内物质组成的变化和功 能的变化。 细胞分化的主要特点包括： 基因表达上的变化，导致组织特异性蛋白的产生； 不同细胞在蛋白质组成上的差异导致细胞结构的不同；改 变其组成就可改变其形状，如MyoD转化； 在细胞分化的早期，不同细胞间的差异难以检测； 分化是渐进过程，进入终端分化的细胞往往不再分裂， 而终端分化后能够继续分裂的细胞可以维持和传递 终端分化状态； 细胞分化由许多细胞外信号(如细胞表面蛋白、分泌蛋白) 控制。 一、概念

Developmental Biology 二、基因活性状恋的可逆性 从单个合子核发育为不同类型细胞, 基因活性谱发生了改变,这种改变是否 涉及遗传物质的改变?

Developmental Biology 二、基因活性状态的可逆性 从单个合子核发育为不同类型细胞， 基因活性谱发生了改变，这种改变是否 涉及遗传物质的改变？

Developmental Biology 1.细胞核移植实验证明: A:分化中遗传物质没有发生不可逆改变 B:细胞质中含有决定核内基因活性谱的控制因子。 Cultured adult skin cells UV radiation destroys DNA in nucleus of fertilized egg Transtcr。 nucleus nto egg Tadpole develops Tadpole gut epithelial cells Removal of nucleus from either cell source Fig 9.2 Nuclear transplantation. The nucleus of an unfertilized the tadpole gut or from cultured aduit skin cells is transferred Xenopus egg is rendered nonfunctional by treatment with ultra into the enucleated egg, and can support the development violet radiation. A nucleus taken trom the epithelial cels lining of an embryo untl at least the tadpole stage 细胞核移植实验也发现,某些类型细胞的核不能代替爪蟾卵 的核,说明这些细胞分化后完全丧失了细胞分裂能力

Developmental Biology 1. 细胞核移植实验证明： A：分化中遗传物质没有发生不可逆改变； B：细胞质中含有决定核内基因活性谱的控制因子。 细胞核移植实验也发现，某些类型细胞的核不能代替爪蟾卵 的核，说明这些细胞分化后完全丧失了细胞分裂能力

Developmental Biology Dolly and her foster mother

Developmental Biology Dolly and her foster mother

Developmental Biol 动物克隆的程序 Cloning a sheep-the creation of Dolly Donar Ewe body cell from an adult female sheep to create a genetically Egg Provide dentical lamb named Dolly This achievement marked the first time that researchers had produced a specialied cell from an adult vertebrate (animal voth a ackbone). variations of the technique pioneered by the Scottish scientists were ixing uscd af other laboratories in 1999 in researc:h on cloning cattle and other animals. 1. A specialized ud- der cell from a ewe was placed in a so- 2. A thin pipette was cleus icontaining the ecome non- 3. The cells genes) from the agn cell fused with a spark 4. The resulting cell con- genes)of the donor dder oll and the oute 5. The cell grew into an embryo owering of the egg providers cell ed in a surrogate mother's womb Dolly the Cinn 6. The surrogate mother gave natic duplicate, or clone, of the donor eive

Developmental Biology 动物克隆的程序

Developmental Biology 2.细胞融合实验也证明了分化中遗传物质改变的可逆性 A:人肝细胞与大鼠肌细胞的融合实验 Huma Fig. 9. 4 Cell fusion shows the liver cell Rat muscle cell reversibility of gene inactivation during differentiation. A human liver ell is fused with a rat muscle cell. the exposure of the human nucleus(red) to the rat muscle cytoplasm results in the activation of muscle-specific repression of liver-specific genes in the human nucleus, Human muscle proteins Human liver cell and rat muscle cell fused are made together with rat muscle proteins This shows that the inactivation of muscle specific genes in human liver cells is not reversible Activation of human muscle gene expression Rat and human muscle proteins are produced oi--.6

Developmental Biology 2. 细胞融合实验也证明了分化中遗传物质改变的可逆性 A：人肝细胞与大鼠肌细胞的融合实验

Developmental biology 3.细胞分化状态是可以改变的 eg,两栖类肢体再生中肌细胞可转变为骨细胞;鸡视网膜表皮色素 细胞在含透明质酸酶、血清、苯硫脲的条件下培养后转变为晶体状细 胞 Fig 9.5 Transdifferentiation of retinal serum, and phenylthiourea, they lose pigment cells. A single pigmented their pigment and retinal cell character- epithelial cell from the embryonic chick istics. If cultured at a high density with retina can be grown in culture to produce ascorbic acid. they differentiate as lens a monolayer of pigmented cells. On further cells and produce the lens-specific protein culture in the presence of hyaluronidase, crystallin. After Okada, T.S.: 1992 Single differentiated pigmented cell Pigment and retinal cell characteristics lost >~~∠0 Grown in culture Monolayer of pigmented cells Change in culture conditions Transdifferentiate into lens cells Change in culture conditions

Developmental Biology 3. 细胞分化状态是可以改变的 e.g., 两栖类肢体再生中肌细胞可转变为骨细胞；鸡视网膜表皮色素 细胞在含透明质酸酶、血清、苯硫脲的条件下培养后转变为晶体状细 胞

Developmental Biology 三、DNA的不可逆改变导致的细胞分化 eg,脊椎动物免疫系统 Figure 24.3 The pool of immature lymphocytes contains B cells and T cells making antibodies and receptors with a variety of specificities. Reaction with an antigen leads to clonal expansion of the lymphocyte with the antibody (B cell) or receptor T cell) that can recognize the antigen Lymphocyte recognizes antigen Clonal expansi 上 人 人 人

Developmental Biology 三、DNA的不可逆改变导致的细胞分化 e.g., 脊椎动物免疫系统

Developmental Biology Figure 24.1 Overview: humoral immunity is conferred by the binding of free antibodies to antigens Figure 24.2 Overview in cell-mediated immunity. to form antigen-antibody complexes that are remove killer T cells use the T-cell receptor to recognize a from the bloodstream by macrophages or that are fragment of the foreign antigen which is 'presented' attacked directly by the complement proteins on the surface of the target cell by the MHC protein Bcel Secretion of antibodies 寄主细胞MHC by B cell requires helper T cells 进入细胞中的抗原 人AAA (如病毒的肽段) Antbody-antigen comple MHC presents"ant T-cell rece Macrophage T lymphocyte recognize (a complex consisting of-20 proteins

Developmental Biology 进入细胞中的抗原 (如病毒的肽段) 寄主细胞MHC (a complex consisting of ~20 proteins)