Cell differentiation and Cancer cells
Cell differentiation
Chapter 12
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:
1014 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.416,12-1,2n (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
cThe 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?
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,2000,290,1779-1782
Turning brain into blood,Science,1999,283,534-535
NSC+EGF & FGF,Growing
See also,Current opinion in cell
biology,13,662-665,2001
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 tumor Malignant 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,Adenovirus HIV
Benign tumor Malignant tumorNormal cell
3,Caner,As a result of the accumulation of
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-suppressorgene） 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
细胞正常
病毒正常繁殖
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
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."
Dr,Folkman
Cell differentiation
Chapter 12
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:
1014 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.416,12-1,2n (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
cThe 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?
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,2000,290,1779-1782
Turning brain into blood,Science,1999,283,534-535
NSC+EGF & FGF,Growing
See also,Current opinion in cell
biology,13,662-665,2001
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 tumor Malignant 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,Adenovirus HIV
Benign tumor Malignant tumorNormal cell
3,Caner,As a result of the accumulation of
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-suppressorgene） 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
细胞正常
病毒正常繁殖
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
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."
Dr,Folkman
