北京大学：《细胞生物学 Cell Science》课程教学资源（PPT课件讲稿）Cell differentiation

胞科学 ell Science 蔡国平

细胞科学 Cell Science （15） 蔡国平

8 15 Cell differentiation 15.1 Outline The concept of cell differentiation Determination or commitment Totipotency, Pluripotency and Monopotency Developmental landscape model 5.2 Cell differentiation resulting from the expression of specific gene house keeping gene and luxury gene regultory gene and temporal gene 15.3 The genetic control of The cell differentiation 14 4 The influences of environmental factors on cell differentiation 14.5 The maintaining of cell differentiation 14.6 Development and cell differentiation

§ 15. Cell differentiation 15.1 Outline The concept of cell differentiation Determination or commitment Totipotency, Pluripotency and Monopotency Developmental landscape model 15.2 Cell differentiation resulting from the expression of specific genes house keeping gene and luxury gene regultory gene and temporal gene 15.3 The genetic control of The cell differentiation 14.4 The influences of environmental factors on cell differentiation 14.5 The maintaining of cell differentiation 14.6 Development and cell differentiation

Figure 14.2 Formation of blood cells All of the different types of blood cells develop from a pluripotent stem cell Pluripotent stem cell in the bone marrow. The precursors of differentiat ed cells undergo several rounds of cel division as they mature, but cel proliferation ceases at the termi- Myelo nal stages of differentiation Lymphoid o(@◎◎ 必(曝◎ T ly Granulocytes

Figure 14.41 Stem cell proliferation Stem cells divide to form one daughter cell that remains a stem cell and a second that differentiates(e.g, to an intestinal epithelial cell). Stem cel Cell division n Differentiated cell

Growth factor (EGF Plasma membrane Growth factor receptor (ErbB Cytoplasm ERK Fos mRNA 000000 Figure 15.26 Oncogenes and signal transduction Oncogene proteins act as growth factors (e.g, EGF), growth factor receptors(e. g, ErbB), and intracellular signaling mole- cules(Ras and Raf). Ras and Raf activate the ERK mAP kinase pathway(see Fi ures 13.32 and 13.35), leading to the induction of additional genes(e.g. fos)that encode potentially oncogenic transcriptional regulatory proteins. Proteins with known oncogenic potential are highlighted with a yellow glow

Gonad Figure 13.44 Induction of the vulva in C elegans vulva The gonadal anchor cell secretes Lin-3 which is related to EGF. Lin-3 stimu lates Let-23, a receptor protein-tyro Plasma sine kinase expressed by vulval pre cursor cells. Activated Let-23 stimulates the Ras/Raf pathway, which induces three vulval precursor cells to proliferate and differentiate, precursor forming the 22 cells of the vulva Proliteration and 22 cells of the vulva

Figure 13, 42 The Drosophila compound eye (A) Scanning electron micrograph showing the compound eye, com posed of about 800 individual units. Eye Development in drosophila Each unit contains eight photore- tor neurons(designated RI ough R8), which develop in a fixed The development of the compound eye of Drosophila provides a good exam- er and pattern (A Courtesy of T. ple of the role of direct cell-cell signaling in differentiation, which has been ikatesh, University of Michigan. elucidated largely by genetic analysis. The Drosophila compound eye consists of about 800 individual units each of which contains eight photoreceptor neurons (rI through R8)and 12 lens cells(Figure 13.42). The photoreceptor neurons develop in a fixed order, beginning with the differentiation of R8. R8 then induces two neighboring cells to become the R2 and R5 photoreceptors Next, R2 induces neighboring cells to become RI and R3, and R5 induces neighboring cells to become r4 and R6. The final step is differentiation of r7 which is induced by interaction with R8. Lens cells then develop from those cells that do not differentiate into photoreceptors The signaling pathway leading to development of the R7 cell has been characterized in detail, based on the isolation of mutant flies in which r7 fails to develop (Figure 13. 43). One of these mutants(sevenless)results from defects in a gene encoding a receptor protein-tyrosine kinase that is expressed by pre- cursors of R7 cells. Another mutant(called boss, which is short for bride-of-seur enless)results from defects in a gene encoding a cell surface protein expressed by R8 cells. Boss is the ligand for Sevenless, so direct cell-cell interaction 100gm between R8 and a precursor cell activates the sevenless protein-tyrosine kinase. Further studies have shown that cell differentiation induced by sig. RI Rat

Figure 13.40 Early animal development The fer- tilized egg (e. g, of Xenopus laet form a morul ells then undergo extensive arrangements(gastrulation) to form he three germ layers (ectoderm a=○ and cleavage Worli Morula Gcirulation Ernet

Figure 13. 41 Mesoderm induction The Xenopus Ventral Ectoderm egg is divided into animal and vegetal hemispheres. Cells from the animal Animal ole differentiate into ectoderm, and cells from the vegetal pole form endo- derm. In addition, cells from the ani- mal pole can be induced to form meso- vegetal Ventral Dorsal derm in response to factors secreted by endoderm endoderm vegetal pole cells. Fibroblast growth factor(FGF)and activin play key roles in the induction of ventral and dorsal mesoderm, respectively rise to mesoderm instead of ectoderm Further studies of this system have indicated that mesoderm induction mediated hy growth factore that are secreted hy the vegetal nole cells

Growth factor (EGF Plasma membrane Ceptor eRbb MEK Figure 15.26 Oncogenes and signal transduction Oncogene proteins act as growth fact F), growth factor receptors (e. g, ErbB), and intracellular signaling mole- cules(Ras and Raf). Ras and Raf activate the ERK MAP kinase pathway(see Fig- ures 13.32 and 13.35), leading to the induction of additional genes (e.g. fos)that encode potentially oncogenic transcriptional regulatory proteins. Proteins with known oncogenic potential are highlighted with a yellow gl