生物细胞：细胞分化与基因表达调控
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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。
Chapter 12
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
❖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
编辑课件
24
利用干细胞可塑性
Stem cells migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration.
编辑课件
25
Regeneration of new tissues from our own cells will not be far behind
Ras oncogene: Retain bind GTP
Bcl-2 oncogene: Prevent apoptosis
编辑课件
37
(2) Tumor suppressor genes: Loss-of-function mutations
编辑课件
38
Rb gene: The first tumor suppressor gene in patient with retinoblastoma
编辑课件
1
❖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.
Science, December 6, 2002: 1901
编辑课件
26
Cancer: Cells proliferate uncontrollably
Tumor
Benign tumors: Do not spread Malignant tumors — Cancers: Metastasize
transplantation
Transplantation of frog red cell nucleus indicated the nucleus of animal is totipotency(全能性)
编辑课件
10
Dolly: A lamb with no father
The sheep star: Dolly
Carcinogenic chemicals and UV DNA and RNA tumor viruses
Alter the genome
SV40, Adenovirus
HIV
Normal cell Benign tumor Malignant tumor
编辑课件
32
3. Caner: As a result of the accumulation of mutation and natural selection
编辑课件
39
p53: Guardian of the genome
Because the accumulation of gene mutation and Natural selection, so the patient is aged
•
基因属性
细胞增殖必需
•
致癌方式 基因突变激活、异常表达
抑癌基因
细胞分化必需 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
40C
鸡成纤维细胞
37C
细胞正常 细胞癌变
tdRSV
40C
鸡成纤维细胞
37C
细胞正常 细胞正常
编辑课件
病毒正常繁殖
病毒正常繁殖 病毒正常繁殖 病毒正常繁殖
编辑课件
27
Benign tumor
Malignant tumor
编辑课件
28
1. The biology characteristics of cancer
(1) Cell proliferate uncontrollably (2) Invade and metastasize
编辑课件
29
(3) Less well differentiated than normal cells or benign
• Diseases that impair brain function, such as Alzheimer's disease and Parkinson's disease
• Spinal cord injuries • Blood diseases, including leukemias • Burns
tumor cells
(4) Have highly aberrant chromosome complements—
Aneuploidy
Pancreas cancer
编辑课件
30
(5) Lose Contact inhibition in vitro
编辑课件
31
2. The causes of cancer
tdRSV3’端缺失 1500－2000bp;
不影响病毒复制， 但影响细胞转化
v-oncogene
34
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:
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
Turning blood into brain: Science, 2000, 290: 1779-1782
Turning brain into blood: Science, 1999, 283: 534-535 NSC+EGF & FGF: Growing
编辑课件
23
Production of differentiated cells from mouse ES cells in culture.
编辑课件
20
Two ways for a stem cell to produce daughters with different fates
编辑课件
21
4.Why do researchers study stem cells ?
For repairing tissue damage caused by disease or injury, including:
Cancer-inducing mutation genes
Proto-oncogenes Tumor-suppressor genes
编辑课件
33
• 癌基因（oncogenes）：v-onc and c-onc
• 抑癌基因（tumor-suppressor gene）Rb p53
• 特点
原癌基因
编辑课件
3
Cell differentiation occurs in multicellular organisms
Human: 1014 cells, >200 cell types
编辑课件
4
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
编辑课件
5
3. Combinational control and Gene differentiated express
pp.416: 12-1: 2n (n=3, A,B,C)
编辑课件
ቤተ መጻሕፍቲ ባይዱ
6
4. House-keeping genes and luxury genes
The ability of a cell develops into a complete organism
1. Plant cells
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
编辑课件
9
A new organism created
2. Animal cloning— by the process of nuclear
编辑课件
16
3. Types of stem cells: differentiation potential (1) Monopotential stem cell
编辑课件
17
(2) Pluripotent stem cells
编辑课件
18
编辑课件
19
(3) Embryonic stem cells
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）.
编辑课件
35
Proto-oncogenes
编辑课件
36
(1) Proto-oncogens: Gain-of-function mutations
编辑课件
7
5. Transdifferentiation: From one type of cell into another type
Includes: Dedifferentiation---Redifferentiation
去分化
再分化
编辑课件
8
Cell totipotency (细胞全能性)
编辑课件
22
See also: Current opinion in cell
5. Stem cell plasticity
biology, 13: 662-665, 2001
Adult stem cells can differentiate into a large number of different cell types.
编辑课件
13
2. Where to get the stem cells?
(1) Embryonic stem cells
编辑课件
14
(2) Adult stem cells
编辑课件
15
(3) Umbilical cord blood stem cells (4) Fetal stem cells
c
编辑课件
11
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
编辑课件
12
Stem cell and its differentiation potential
1. What is a stem cell ?
Has two abilities:
(1)Self-renewing (2)Differentiating
steps in the pathway from DNA to RNA to protein.
编辑课件
2
The four essential processes by which a multicellular organism is made:
Cell proliferation, Cell specialization, Cell interaction, and Cell movement.
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。
Chapter 12
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
❖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
编辑课件
24
利用干细胞可塑性
Stem cells migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration.
编辑课件
25
Regeneration of new tissues from our own cells will not be far behind
Ras oncogene: Retain bind GTP
Bcl-2 oncogene: Prevent apoptosis
编辑课件
37
(2) Tumor suppressor genes: Loss-of-function mutations
编辑课件
38
Rb gene: The first tumor suppressor gene in patient with retinoblastoma
编辑课件
1
❖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.
Science, December 6, 2002: 1901
编辑课件
26
Cancer: Cells proliferate uncontrollably
Tumor
Benign tumors: Do not spread Malignant tumors — Cancers: Metastasize
transplantation
Transplantation of frog red cell nucleus indicated the nucleus of animal is totipotency(全能性)
编辑课件
10
Dolly: A lamb with no father
The sheep star: Dolly
Carcinogenic chemicals and UV DNA and RNA tumor viruses
Alter the genome
SV40, Adenovirus
HIV
Normal cell Benign tumor Malignant tumor
编辑课件
32
3. Caner: As a result of the accumulation of mutation and natural selection
编辑课件
39
p53: Guardian of the genome
Because the accumulation of gene mutation and Natural selection, so the patient is aged
•
基因属性
细胞增殖必需
•
致癌方式 基因突变激活、异常表达
抑癌基因
细胞分化必需 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
40C
鸡成纤维细胞
37C
细胞正常 细胞癌变
tdRSV
40C
鸡成纤维细胞
37C
细胞正常 细胞正常
编辑课件
病毒正常繁殖
病毒正常繁殖 病毒正常繁殖 病毒正常繁殖
编辑课件
27
Benign tumor
Malignant tumor
编辑课件
28
1. The biology characteristics of cancer
(1) Cell proliferate uncontrollably (2) Invade and metastasize
编辑课件
29
(3) Less well differentiated than normal cells or benign
• Diseases that impair brain function, such as Alzheimer's disease and Parkinson's disease
• Spinal cord injuries • Blood diseases, including leukemias • Burns
tumor cells
(4) Have highly aberrant chromosome complements—
Aneuploidy
Pancreas cancer
编辑课件
30
(5) Lose Contact inhibition in vitro
编辑课件
31
2. The causes of cancer
tdRSV3’端缺失 1500－2000bp;
不影响病毒复制， 但影响细胞转化
v-oncogene
34
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:
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
Turning blood into brain: Science, 2000, 290: 1779-1782
Turning brain into blood: Science, 1999, 283: 534-535 NSC+EGF & FGF: Growing
编辑课件
23
Production of differentiated cells from mouse ES cells in culture.
编辑课件
20
Two ways for a stem cell to produce daughters with different fates
编辑课件
21
4.Why do researchers study stem cells ?
For repairing tissue damage caused by disease or injury, including:
Cancer-inducing mutation genes
Proto-oncogenes Tumor-suppressor genes
编辑课件
33
• 癌基因（oncogenes）：v-onc and c-onc
• 抑癌基因（tumor-suppressor gene）Rb p53
• 特点
原癌基因
编辑课件
3
Cell differentiation occurs in multicellular organisms
Human: 1014 cells, >200 cell types
编辑课件
4
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
编辑课件
5
3. Combinational control and Gene differentiated express
pp.416: 12-1: 2n (n=3, A,B,C)
编辑课件
ቤተ መጻሕፍቲ ባይዱ
6
4. House-keeping genes and luxury genes
The ability of a cell develops into a complete organism
1. Plant cells
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
编辑课件
9
A new organism created
2. Animal cloning— by the process of nuclear
编辑课件
16
3. Types of stem cells: differentiation potential (1) Monopotential stem cell
编辑课件
17
(2) Pluripotent stem cells
编辑课件
18
编辑课件
19
(3) Embryonic stem cells
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）.
编辑课件
35
Proto-oncogenes
编辑课件
36
(1) Proto-oncogens: Gain-of-function mutations
编辑课件
7
5. Transdifferentiation: From one type of cell into another type
Includes: Dedifferentiation---Redifferentiation
去分化
再分化
编辑课件
8
Cell totipotency (细胞全能性)
编辑课件
22
See also: Current opinion in cell
5. Stem cell plasticity
biology, 13: 662-665, 2001
Adult stem cells can differentiate into a large number of different cell types.
编辑课件
13
2. Where to get the stem cells?
(1) Embryonic stem cells
编辑课件
14
(2) Adult stem cells
编辑课件
15
(3) Umbilical cord blood stem cells (4) Fetal stem cells
c
编辑课件
11
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
编辑课件
12
Stem cell and its differentiation potential
1. What is a stem cell ?
Has two abilities:
(1)Self-renewing (2)Differentiating
steps in the pathway from DNA to RNA to protein.
编辑课件
2
The four essential processes by which a multicellular organism is made:
Cell proliferation, Cell specialization, Cell interaction, and Cell movement.