Cell differentiation and Cancer cells Cell differentiation 1. About the concept of cell differentiation The process that a cell changes to carry out a specialized function: Marked by: Morphology / Structure / Function

 The different cell types of a multicellular organism contain the same DNA.  A cell can change the expression of its genes in response to external signals.  Differences in mRNA expression patterns among different cell types.  Different cell types synthesize different sets of proteins.  Gene expression can be regulated at many of the steps in the pathway from DNA to RNA to protein.

The four essential processes by which a multicellular organism is made: Cell proliferation, Cell specialization, Cell interaction, and Cell movement.

Cell differentiation occurs in multicellular organisms Human: cells, >200 cell types

2. Why a fertilized egg can develop into different cells: Gene differentiated express 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: 2 n (n=3, A,B,C)

4. House-keeping genes and luxury genes House-keeping genes: Expressed in all cell types, essential for all cells Luxury genes: Tissue-specific genes, expressed in special cells Sequential expression of various genes in early Drosophila embryo

5. Transdifferentiation: From one type of cell into another type Includes: Dedifferentiation---Redifferentiation 去分化再分化

Cell totipotency ( 细胞全能性 ) 1. Plant cells The 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 cloning— Transplantation of frog red cell nucleus indicated the nucleus of animal is totipotency( 全能性 ) A new organism created by the process of nuclear transplantation

Dolly: A lamb with no father c The sheep star: Dolly

克隆能给人类带来什么？ 克隆动物是未来的制药厂 克隆的爱因斯坦会懂 “ 相对论 ” 吗

Stem cell and its differentiation potential 1. What is a stem cell ? 1. What is a stem cell ? Has two abilities: (1)Self-renewing (2)Differentiating

2. Where to get the stem cells? (1) Embryonic 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 cells

Two ways for a stem cell to produce daughters with different fates

4.Why do researchers study stem cells ? For repairing tissue damage caused by disease or injury, including: Diseases that impair brain function, such as Alzheimer's disease and Parkinson's disease Spinal cord injuries Blood diseases, including leukemias Burns

5. Stem cell plasticity Adult stem cells can differentiate into a large number of different cell types. Turning blood into brain: Science, 2000, 290: Turning brain into blood: Science, 1999, 283: NSC+EGF & FGF: Growing See also: Current opinion in cell biology, 13: , 2001

Production of differentiated cells from mouse ES cells in culture.

Stem cells migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration. 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: 1901

Cancer: Cells proliferate uncontrollably Tumor Benign tumors: Do not spread Malignant tumors — Cancers: Metastasize

Benign tumorMalignant tumor

1. 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— Aneuploidy Pancreas cancer

(5) Lose Contact inhibition in vitro

2. The causes of cancer Carcinogenic chemicals and UV DNA and RNA tumor viruses Alter the genome SV40, AdenovirusHIV Benign tumorMalignant tumorNormal cell

3. Caner: As a result of the accumulation of mutation and natural selection mutation and natural selection Cancer-inducing mutation genes Proto-oncogenes Tumor-suppressor genes

 癌基因（ oncogenes ）： v-onc and c-onc 抑癌基因（ tumor-suppressor gene ） Rb p53 特 点 原癌基因 抑癌基因 基因属性 细胞增殖必需 细胞分化必需 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 40C 37C 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 40C 37C 细胞正常 病毒正常繁殖 v-oncogene tdRSV3’ 端缺失 1500 － 2000bp; 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 c-onc 的关系： c-onc 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（ Rb—13q14.1 ）.

Proto-oncogenes

(1) Proto-oncogens: Gain-of-function mutations Ras oncogene: Retain bind GTP Bcl-2 oncogene: Prevent apoptosis

(2) Tumor suppressor genes: Loss-of-function mutations Loss-of-function mutations

Rb gene: The first tumor suppressor gene in patient with retinoblastoma

p53: Guardian of the genome Because the accumulation of gene mutation and Natural selection, so the patient is aged

Chart of the major signaling pathways relevant to cancer in human cells, indicating the cellular locations of some of the proteins modified by mutation in cancers.

Can we treat cancer? 1. Conventional approaches to combating cancer Surgery Chemotherapy/Radiation Can not rid of all cancer cells

2. Gene therapy Tumor cells lack functional tumor-suppressor genes p53-bearing viruses Engineered adenovirus Immune response

3. Inhibiting the formation of blood vessels Angiogenesis: Cancer cells — growth factors — endothelial cells — form new vessels

Dr. Folkman’s 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." "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 Dr. Folkman