胚胎學

胚胎及發育生物學

Embryogenesis, Developmental Biology and Stem Cell

中山大學

中山大學

生物科學系

生物學中最有趣的是甚麼問題??

生物多樣性

生物多樣性

與

生命現象

生命現象

3

Genetics and Evolution

•

Variation

Variation

in the DNA sequence makes it possible for species to

in the DNA sequence makes it possible for species to

evolve over time.

•

Organisms with similar DNA sequences are descended from a

common ancestor

.

4

生物為何那樣多樣性?

_{化繁為簡(小處著手)}

生物學中最有趣的是甚麼問題??

生物多樣性

與

生命現象

生命現象

7

解剖(胚胎)學/ 個體生物(生理)學 細胞生物學 染色體/DNA

生命現象的研究

胚胎學上古老的爭論

解剖(胚胎)學/ 個體生物(生理)學 - 細胞生物學- 染色體/DNA 遺傳學

Preformation theory (先成說)

胚胎的各部份是一開始就存在?

Epigenesis theory (漸成說)

胚胎學上古老的爭論

Epigenesis theory (漸成說)

還是在發育過程中逐漸形成的？

An homunculus in the head of each sperm (1694)

生物學中最有趣的是甚麼問題??

生物多樣性 與 生命現象

生物化學 動 (低-高) 植 (低-高) 微生 病毒 生物化學 解剖(胚胎)型態 生理 細胞生物 病毒 生物-環境 細胞生物 分子生物 發育生物 9

胚胎發育及幹細胞

胚胎發育及幹細胞

vein ISV CVP S

胚胎

幹細胞

複製/再生

幹細胞

Outline

Outline

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

2

模式生物 (

d l

i

)

2.

模式生物 (model organisms)

3.

動物發育的主要階段

4.

發育過程之機制

5.

組織再生與幹細胞

胚胎學 (Embryology) : The development of an embryo from the fertilized egg

發育生物學 (Developmental Biology) is to understand how multicellular organism develop

偏重述敘的科學, 探討如何形成個體正確及完整形態的各個步驟。

着重於分子和细胞生物學層次上的胚胎學。

何謂發育生物學？

何謂發育生物學？

‧發育生物學(developmental biology) 源自於胚胎學

p

gy

(embryology)

‧胚胎學：探討受精卵到出生的過程

胚胎學：探討受精卵到出生的過程

(

A Body-Building Plan)

‧發育生物學包含：

胚胎學

+

個體生長、器官及組織受損的修復與再

生、 老化、疾病的發生與治療等

胚胎學上古老的爭論

Preformation theory (先成說)

胚胎學上古老的爭論

Preformation theory (先成說)

Epigenesis theory (漸成說)

Epigenesis theory (漸成說)

胚胎的各部份是 開始就存在?

胚胎的各部份是一開始就存在?

還是在發育過程中逐漸形成的？

An homunculus in the head of each sperm (1694)

Malpighi’s description of the chick embryo. (1673)

顯微鏡的發明

細胞學說的確立 (1820-1880)

基因概念的形成 (1900)

基因概念的形成 (1900)

發育的三要素:

1. 生長/分裂 growth/cleavage

g

g

Increase in cell number Increase in cell size

2. 分化 Differentiation

The fate of daughter cells

3. 形態發生 Morphogenesis

發育的三要素:

發育的三要素:

1. 生長/分裂 growth/cleavage

g

g

Increase in cell number Increase in cell size

2. 分化 Differentiation

The fate of daughter cells

3. 形態發生 Morphogenesis

發育生物學的 (研究)中心主題

細胞如何分化成特定種類？

發育生物學的 (研究)中心主題:

細胞如何分化成特定種類？

細胞如何移動到特定位置？

如何控制這些細胞發育成為不同類型的細胞組織？

細胞如何分化成特定種類？

What happen if genetic control goes wrong in

pp

g

g

g

limb development?

1. 了解動物胚胎的發育(分子機制)

l

d

d

d d

germ layers: ectoderm, mesoderm, endoderm

organogenesis

2. 了解發育生物學的研究發展及重要性

母體-胎兒保健 預防新生兒缺陷

3 發育生物學的相關應用

母體 胎兒保健, 預防新生兒缺陷

3. 發育生物學的相關應用

a.幹細胞 b.複製及器官再生 c.細胞凋零 d.老化 e. 癌症與疾病

Model organisms to study developmental biology

模式生物

模式生物

– nematode (C. elegans) – fruit fly (D. melanogaster )

線蟲 果蠅

fruit fly (D. melanogaster ) – sea urchins

– South African Frog (X. laevis) – Zebrafish (D. Renio) 果蠅 海膽 ( ) – chick – mouse

– plant (A. thaliana)

Universal mechanisms of animal development

通用機制

小腦 通用機制

Drosophila with mutant

alleles of the eyeless Mouse embryos with wild-type (L) and mutant (R) alleles of the Pax-6 gene

Fig. Homologous proteins functioning interchangeably in the development of mice and flies.

y

人類不利於作發育 疾病模式之原因

人類不利於作發育, 疾病模式之原因：

• 1.壽命長。

.壽命長

• 2.再生時間緩慢。

• 3.子代少。

極度異質性

• 4.極度異質性。

• 5.無法長期控制飼養方式及社經生活。

• 6 定量資料如飲食、飼養方面缺乏。

• 6.定量資料如飲食、飼養方面缺乏。

• 7.道德上的問題。

Comparative anatomy and Embryology provide clues to animal phylogeny M “Porifera” 刺胞 演化樹: 比較解剖學 ANCESTRAL COLONIAL FLAGELLATE etazoa Eum e Cnidaria Ctenophora 刺胞 e tazoa Deuter o Ectoprocta Brachiopoda B o stomia Echinodermata Ch d (後口) 棘皮 sea urchin notochord 脊索 B ilateria P Chordata Platyhelminthes 脊索 (後口) 扁型 mammal ascidians vertebrate 脊椎(骨) P rotosto m Rotifera Mollusca 扁型 輪型 軟體 m ia Annelida (原口) 軟體 環節 Arthropoda Nematoda 節肢 insect worm

nematode (Caenorhabditis elegans)

3d

線蟲

15hr 3d 50h 50hr

Zygote

0

First cell division

rs) Nervous system, t ki Muscula-ture, gonads Germ line (future t ) Outer skin, nervous system ation (hou

ABa ABp EMS P2 P3

P4 outer skin, muscula-ture gametes) Musculature fter fertiliz Hatching 10 Ti m e a Intestine Hatching Mouth Intestine E V l Anus Eggs Vulva 1.2 mm ANTERIOR POSTERIOR

Zygote

0

First cell division

rs) Nervous system, t ki Muscula-ture, gonads ation (hou

ABa ABp EMS P2 P3

Germ line (future t ) Outer skin, nervous system P4 Pharynx Intestine outer skin, muscula-ture fter fertiliz gametes) Musculature Hatching 10 Ti m e a Hatching Intestine Vulva Epidermis Somatic gonad Mouth Intestine E V l Anus g Eggs Vulva 1.2 mm ANTERIOR POSTERIOR

fruit fly (Drosophila melanogaster )

果蠅

~10d 5d 3hr 12-24hr

Body plan: To build a body

bicoid (前後) (頭尾) nanos torso hunchback (頭胸腹) hunchback Kruppel knirp 7 (頭胸腹) giant even-skipped fushi tarazu 14 (區域/節) hairy engrailed h d h (小區域/節也 要分前後) hedgehog frizzled patched Ultrabithorax

Adult fruit fly

Fruit fly embryo (10 hours) Fly Fly chromosome Mouse Homeobox genes Mouse chromosomes Mouse embryo (12 days) Adult mouse

Adult fruit fly

Fruit fly embryo (10 hours) Fly Fly chromosome Mouse Homeobox genes Mouse chromosomes Mouse embryo (12 days) Adult mouse

模式生物

模式生物

– nematode (Caenorhabditis elegans)

nematode (Caenorhabditis elegans)

– fruit fly (Drosophila melanogaster )

–

sea urchins

sea urchins

海膽

– South African Frog (Xenopus laevis)

– Zebrafish (Danio Renio)

海膽

Zebrafish (Danio Renio)

– chick

– mouse

mouse

– plant (Arabidopsis thaliana)

Sea urchin

經典的動物發育研究材料之一 radically symmetrical adult Fertilization Cleavage Cleavage

Three germ layers /gastrulation

bilaterally symmetrical free-swimming larva

The sea-urchin embryo develops into a free-swimming larva The sea-urchin embryo develops into a free-swimming larva

Development of the sea urchin embryo.

symmetric animal-vegetal_{asymmetricasymmetric} hollow

骨棒(中胚層)

初級間質 _{gut invaginate}

二級間質

Blue: prospective ectoderm

Yellow: endoderm

模式生物

模式生物

– nematode (Caenorhabditis elegans)

nematode (Caenorhabditis elegans)

– fruit fly (Drosophila melanogaster )

– sea urchins

無脊椎

sea urchins

– South African Frog (Xenopus laevis)

– Zebrafish (Danio Renio)

無脊椎

Zebrafish (Danio Renio)

– chick

– mouse

mouse

– plant (Arabidopsis thaliana)

Zebrafish (Danio Renio)

3mo

24hr heart beat 24hr heart beat

模式生物

模式生物

– nematode (Caenorhabditis elegans)

nematode (Caenorhabditis elegans)

– fruit fly (Drosophila melanogaster )

– sea urchins

sea urchins

– South African Frog (Xenopus laevis)

– Zebrafish (Danio Renio)

Zebrafish (Danio Renio)

– chick

– mouse

mouse

– plant (Arabidopsis thaliana)

Part 3 Life cycle of the chicken

2 layers

Bi d d l bl h th d diff t f f i i t t

extra-embryonic structures

Birds and mammals resemble each other and different from frog in some important features of early development

Fig. 47-11

Dorsal Fertilized egg

Anterior Primitive _streak

Anterior Right Left Embryo Yolk streak Ventral Posterior Primitive streak Yolk Epiblast Primitive streak Future ectoderm Epiblast ectoderm Endoderm Migrating cells Hypoblast Blastocoel (mesoderm) _YOLK

The extra-embryonic structure and circulation of the chick embruyo 羊膜 4 days 絨毛膜 絨毛膜 尿囊

Amnion and amniotic cavity provide mechanical protection Chorion maintain shell

具羊膜 (與哺乳類像)

Chorion maintain shell

Allantois bridge for oxygen and waste

Vitelline vein take nutrient form yolk to embryo Umbilical vein take oxygen to embryo

mouse

_缺點?

模式生物(動物)的特性

模式生物(動物)的特性

1.

與人類有相似處 (功能相似, 有基因保留性)

2.

易培養 (經費少, 空間小, 生長周期短, 繁殖快, 子代多)

3

易於實驗操作 (體外受精 胚體透明 容易進行基因操控)

3.

易於實驗操作 (體外受精, 胚體透明, 容易進行基因操控)

4.

資料多 (基因已解碼)

Primate

Primate

黑猩猩: HIV, HBV,

Behavior, Learning

,

g

O tline

Outline

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

2.

模式生物 (model organisms)

2.

模式生物 (model organisms)

3.

動物發育的主要階段

4.

發育過程之機制

5

組織再生與幹細胞

5.

組織再生與幹細胞

動物發育的主要階段

動物發育的主要階段

所有動物皆一樣?

所有動物皆一樣?

動物發育的主要過程

動物發育的主要過程

1.受精 (Fertilization)

2.卵裂 (Cleavage)

3.原腸化 (Gastrulation)

cell division creates a hollow ball of cells called a blastula

cells are rearranged into a three layered gastrula

4.神經 (Neurulation)

cells are rearranged into a three-layered gastrula

5.器官生成 (Organogenesis)

th th l i t t d t i i t

6.個體生成 (Growth)

Fertilization

F tili

ti

b i

th h

l id

l i f

d

• Fertilization brings the haploid nuclei of sperm and

egg together, forming a diploid zygote

• The sperm’s contact with the egg’s surface

initiates metabolic reactions in the egg that trigger

the onset of embryonic development

含酵素以分解卵表面膠質層 含酵素以分解卵表面膠質層

The acrosomal and cortical reactions during sea urchin fertilization

Sperm plasma Acrosomal Sperm nucleus membrane Fertilization Basal body (centriole) Sperm Acrosomal process Actin filament envelope Sperm head Fused plasma membranes Cortical granule Sperm-binding Acrosome

Jelly coat _{Vitelline layer}

Egg plasma Hydrolytic enzymes membranes Perivitelline space p g

動物發育的主要過程

動物發育的主要過程

1 受精 (F tili ti )

1.受精 (Fertilization)

2.卵裂 (Cleavage)

3 原腸化 (G t l ti )

3.原腸化 (Gastrulation)

4.神經 (Neurulation)

5 器官生成 (O

i )

5.器官生成 (Organogenesis)

6.個體生成 (Growth)

Cleavage

_blastocoel(囊胚腔)

Cleavage in a frog embryo

Animal

l

8-cell

stage

pole

Vegetal

l

pole

Cleavage in a frog embryo

Blastocoel

Blastula

(cross

(cross

section)

0.25 mm 0.25 mm

Cleavage in a frog embryo

0.25 mm 0.25 mm

Blastocoel

Animal pole

4

2

ll

Zygote

₈

Vegetal

_Blastula

(cross

section)

4-cell

stage

forming

2-cell

stage

forming

Zygote

_8-cell

stage

pole

)

g

g

Right

Dorsal

The body axes and their

establishment in an amphibian

Posterior Anterior

establishment in an amphibian

體軸 Left 體軸 前/後軸(A/P axis) 背/腹軸(D/V axis) 左/右軸(L/R axis)

(a) The three axes of the fully developed embryo Ventral ( ) Pigmented cortex First cleavage Animal pole Animal hemisphere Point of sperm nucleus Future dorsal side nucleus entry Gray crescent Vegetal hemisphere Vegetal pole

(b) Establishing the axes Vegetal pole

Fig. 47-23b Experimental egg Control egg EXPERIMENT Experimental egg (side view) Gray Control egg (dorsal view) Gray crescent G ay crescent Thread Thread RESULTS RESULTS Normal Belly piece Normal

動物發育的主要過程

動物發育的主要過程

1 受精 (F tili ti )

1.受精 (Fertilization)

2.卵裂 (Cleavage)

3 原腸化 (G t l ti )

3.原腸化 (Gastrulation)

4.神經 (Neurulation)

5 器官生成 (O

i )

5.器官生成 (Organogenesis)

6.個體生成 (Growth)

大量細胞轉移

胚層生成

胚層生成

體軸建立

Gastrulation in a sea urchin embryo

原腸化 原腸化

外胚層

Future ectoderm Future endoderm Future mesoderm A h t

中胚層

內胚層

Blastocoel Archenteron Blastopore Blastocoel Blastocoel Archenteron Animal pole Filopodia pulling archenteron tip Mouth Ectoderm Mesenchyme cells Vegetal plate Vegetal_l Digestive tube (endoderm) Mouth Mesenchyme (mesoderm forms future skeleton) Blastopore Mesenchyme cells plate _pole 50 µm skeleton) Anus (from blastopore)

SURFACE VIEW Animal pole

CROSS SECTION

Gastrulation in the frog

Blastocoel

Dorsal lip of

blasto-Dorsal lip

– Cells of the dorsal lip originate in the gray crescent and

Vegetal pole Early

gastrula

Blastopore

pore Dorsal lip of blastopore

in the gray crescent and

invaginate to create the archenteron

Cells continue to move by

Blastocoel

shrinking Archenteron

– Cells continue to move by

involution

– These cells become the

d d d d

endoderm and mesoderm

– The blastopore encircles a

yolk plug when gastrulation is

l t d

Ectoderm Mesoderm

completed

– ectoderm, endoderm, and

mesoderm Key Blastocoel remnant Archenteron Mesoderm Endoderm Future ectoderm Key Future endoderm

Future mesoderm Late gastrula

Blastopore

Mammal (human)

Maternal blood l Endometrial epithelium (uterine lining)

Inner cell mass

Uterus vessel Trophoblast Blastocoel 羊膜 Amnion Chorion Ectoderm 絨毛膜 羊膜 Yolk sac Mesoderm Endoderm Extraembryonic mesoderm Allantois 尿囊 尿囊

動物發育的主要過程

動物發育的主要過程

1 受精 (F tili ti )

1.受精 (Fertilization)

2.卵裂 (Cleavage)

3 原腸化 (G t l ti )

3.原腸化 (Gastrulation)

4.神經 (Neurulation)

5 器官生成 (O

i )

5.器官生成 (Organogenesis)

6.個體生成 (Growth)

Neural folds Tail bud N l l Somites Eye

neurulation

(神經管的生成) Neural fold Neural plate 1 SEM Neural fold Neural plate Neural tube Notochord 1 mm 1 mm SEM Neural crest cells 神經板 Neural crest cells Notochord Coelom _Somite 脊索 Neural crest cells Outer layer of ectoderm Mesoderm Ectoderm Endoderm _{(c) Somites} Archenteron (digestive cavity) 神經脊細胞 Neural tube cells Archenteron

(a) Neural plate formation

動物發育的主要過程

動物發育的主要過程

1 受精 (F tili ti )

1.受精 (Fertilization)

2.卵裂 (Cleavage)

3 原腸化 (G t l ti )

3.原腸化 (Gastrulation)

4.神經 (Neurulation)

5 器官生成 (O

i )

5.器官生成 (Organogenesis)

6.個體生成 (Growth)

ECTODERM MESODERM ENDODERM

外胚層

中胚層

內胚層

ECTODERM MESODERM ENDODERM

Epidermis of skin and its derivatives (including sweat glands hair follicles)

Notochord Skeletal system Muscular system Epithelial lining of digestive tract Epithelial lining of glands, hair follicles)

Epithelial lining of mouth and anus

Cornea and lens of eye

Muscular system Muscular layer of

stomach and intestine Excretory system

Epithelial lining of respiratory system

Lining of urethra, urinary bladder, and reproductive Nervous system

Sensory receptors in epidermis

Adrenal medulla

Circulatory and lymphatic systems

Reproductive system (except germ cells)

system Liver Pancreas Thymus Tooth enamel

Epithelium of pineal and pituitary glands

( p g )

Dermis of skin

Lining of body cavity Adrenal cortex

y

Thyroid and parathyroid glands

Germ Layers:

外

Ectoderm,

Mesoderm,

Endoderm

外胚層

中胚層

Endoderm

_內胚層

Organogenesis

Limb Limb Expression of

thalidomide

「沙利竇邁」 在1997年，統計發現人類的新生兒中有2%的是畸形，這些缺陷的產生，有些是來自基因，另外的大 宗，可能來自環境因子抑制了發育的過程。以1961年Lenz和Mcbride發現為例，他們證明一種用來鎮定孕婦 憂鬱的藥(thalidomide)，會使新生兒四肢發育不全。Nowack(1965)研究發現，這藥物會在懷孕初期的20~36 憂鬱的藥(thalidomide)，會使新生兒四肢發育不全。Nowack(1965)研究發現，這藥物會在懷孕初期的20~36 天左右，對四肢的發育產生抑制的作用，當時藥物包括台灣的遠東地區都有販售，因此可看見現年約 40~50歲世代，有許多這樣的例子出現，造成許多悲劇與社會的成本，

Branching morphogenesis

g

p

g

of lung

g

mediated by FGF10 and Shh signaling

kidney

後腎母細胞 後腎母細胞

輸尿管

Blood vessels

S h

ti

f h

h

t d

l

t

Schematic of human heart development

Ventricle (心室) 主 肺 Atrium (心房) 僧帽瓣 尖瓣 Looping and partitioning 三尖瓣 Left side: Pitx2

BMP Nkx2.5 Transcription factor Retinoic acid

GATA

(7 activating regions and 3 repressor regions)

GATA

Organ handedness in vertebrates

In the mouse, the iv gene controls the handedness of internal organs.

In iv mutants, organ handedness is random and some individuals show, g

heterotaxis where normal and inverted organs are found in one animal.

Heterotaxis (內臟易位): The organs of inverted normal and asymmerty are present in the same animal

Normal iv mutant

The condition, situs inversus, found in 1 in 10,000 people, is a mirror reversal of the 'handedness' of the internal organs

of the handedness of the internal organs.

器官轉位

Situs inversus causes the positions of the heart and lungs to be mirrored.

心臟偏左, 肺葉左二,右三葉, 腹腔右邊的器官是肝臟, 膽囊, 兩邊都是右邊的臟器 器官整個左右相反 腹腔右邊的器官是肝臟, 膽囊, 腹腔左側的器官是脾臟, 胃

The condition, situs inversus, found in 1 in 10,000 people, is a mirror reversal of the 'handedness' of the internal organs

of the handedness of the internal organs.

Situs inversus causes the positions of the heart and lungs to be mirrored.

心臟偏左, 肺葉左二,右三葉, 腹腔右邊的器官是肝臟, 膽囊, 兩邊都是右邊的臟器 器官整個左右相反 腹腔右邊的器官是肝臟, 膽囊, 腹腔左側的器官是脾臟, 胃

動物發育的主要過程

動物發育的主要過程

1.受精 (Fertilization)

卵裂

2.卵裂 (Cleavage)

3.原腸化 (Gastrulation)

神經

4.神經 (Neurulation)

5.器官生成 (Organogenesis)

個體生成

h

6.個體生成 (Growth)

Pattern/ hair, spots, stripe

?

?

Outline

Outline

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

2

模式生物 (

d l

i

)

2.

模式生物 (model organisms)

3.

動物發育的主要階段

4.

發育過程之機制

5.

組織再生與幹細胞

發育過程包括

Pattern formation

(body plan)

Morphogenesis (型態)

Morphogenesis (型態)

Cell differentiation (分化)

Growth (生長)

4

發育過程之機制

體軸 前/後軸(A/P axis) 背/腹軸(D/V axis)

Growth (生長)

4.

發育過程之機制

2 C ll f t d t

i

ti

細胞命運決定

1. Differential gene expression/signaling (基因表現)

左/右軸(L/R axis)

2. Cell fate determination 細胞命運決定

3. Induction 誘導

4 Pattern formation

4. Pattern formation

a. Positional information

b. Lateral inhibition

5. Asymmetric division (不對稱分化)

4.1. Differential gene expression causes

cell differentiation

cell differentiation

Representative cell types of a vertebrate

人類有100億cells, 250種不同類型的細胞 線蟲952 cells.

Gene expression and protein synthesis

p

p

y

In the early development of Drosophila at least 60 genes are In the early development of Drosophila, at least 60 genes are directly involved in pattern formation to form segments.

In C. elegant, at least 50 genes are needed to specify vulva (reproductive structure). About 9% of the genes (1722/ 20,000) are involved in development.

Development of the sea urchin embryo.

symmetric animal-vegetal_{asymmetricasymmetric} hollow

骨棒(中胚層)

初級間質 _{gut invaginate}

二級間質

Blue: prospective ectoderm

Yellow: endoderm

Study (tracking) gene expression in embryos

SOX10

4.2. Cell fate determination

Cell transplantation

earlier stage: not determined

2. Cell fate determination

Cell-linage analysis Principles of Development 4e Wolpert/Tickle Copyright © 2011 by Oxford University Press

4. 2. Cell fate determination

3. Induction

One group of cells could determine the development of neighboring cellsp g g

Spemann and Mangold experiment

The vertebrate eye develops from the neural

tube and the ectoderm of the head

tube and the ectoderm of the head

out layer of optic vesicle Lens detach Inner layer of optic vesicle Pigmented epithelium from forebrain Lens detach from ectoderm

Fig. The main stages in the development of the vertebrate eyes

invagination Induce lens formation _{Overlying ectoderm} form cornea

4. Pattern formation

4. Pattern formation

a Positional information

cell-cell communication

a. Positional information

cell cell communication

Morphogen (生長因子) Morphogen gradient a b b Set >a : Blue

Synpolydactyly (SPD), caused by

mutations in HOXD 13 is characterized

Mutations that affect antero-posterior patterning can cause mutations in HOXD 13, is characterized

by extra fingers and toes and bone abnormalities in the hands and feet

posterior patterning can cause polydactyly. With preaxial

polydactyly has mutations in the

SHH gene SHH gene

4. Pattern formation (spacing patterns)

( p

g p

)

b. Lateral inhibition

5. Asymmetric division

Cytoplasmic determinant

germline cell marker (green)

Cell nuclear (blue) Cell nuclear (blue)

Outline

Outline

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

2

模式生物 (

d l

i

)

2.

模式生物 (model organisms)

3.

動物發育的主要階段

4.

發育過程之機制

The capacity for regeneration in urodele amphibians (newt)( )

(1) Dorsal crest, (2) limbs, (3,4) retina and lens, (5) jaw, and tail

Principles of Development 4e

Wolpert/Tickle Copyright © 2011 by Oxford

幹細胞

幹細胞

1.甚麼是幹細胞

2.幹細胞來源

a. 成體幹細胞 (adult stem cell):

(

)

骨髓，成體週邊血 (取得極為困難）

b 胚胎幹細胞 (embryonic stem cell):

b. 胚胎幹細胞 (embryonic stem cell):

胚胎，臍帶血 (取得容易)

3 幹細胞之運用 (複製 組織再生)

3. 幹細胞之運用 (複製, 組織再生)

4. 幹細胞研究之道德探討

What Are Stem Cells?

• Stem cells share two basic characteristics that make

them distinctive from other cell types : self-renewal and

differentiation into specialized cell types

human embryonic stem cells (hESCs)

幹細胞來源之一

胚胎幹細胞

human embryonic stem cells (hESCs)

Cell differentiation (細胞分化)

How to control the cell differentiation? differential expression of gene?

Can differentiated cells reverse to ES cells? 返老還童?

Promoter—coding region

SCNT iPS

S

omatic

C

ell

N

uclear

T

ransfer (

體細胞核移殖)

複製動物

SCNT

複製動物

•1997年2月27日英國Roslin

研究所科學家於Nature雜

誌上首先發表複製羊桃莉

(Dolly)複製成功

Nature 385: 810 Nature 385: 810

Somatic cell nuclear transplantation (SCNT)

by John Gurdon

山中伸彌「誘導式多能性幹細胞」

iPS (induced pluripotent stem cells)

複製人與器官複製

2n n

病

inner cell 代理孕母 體外培養 2n 幹細胞 inner cell mass

X

(分裂) 生命之開始 合法？合理？ 幹細胞 (分化) 命之 始 (法律定義) 合法？合理？

組織工程(Tissue Engineering)

• 皮膚移植（燒燙傷、美容） • 器官再造

– 1997 Dr. Charles Vacanti (University of Massachusetts)( y )

利用小鼠製造人工義耳: 以可吸收性聚合物製造耳朵形狀，以牛 膠原細胞包覆, 埋放到裸鼠皮下，生長成人形耳朵 – 其他可能應用：膀胱、軟骨、血管…等 Principles of Development 4e Wolpert/Tickle Copyright © 2011 by Oxford University Press

• Scientists working in regenerative medicine are also optimistic about their

regenerative medicine (再生醫學)

• Scientists working in regenerative medicine are also optimistic about their

ability to produce viable organs from stem cells

• Sheets of skin and other organs such as the urinary bladder have been

created in vitro created in vitro Principles of Development 4e Wolpert/Tickle Copyright © 2011 by Oxford University Press

QUESTIONS?

Summary

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

1.

胚胎學 (embryology) vs. 發育生物學 (developmental biology)

2.

模式生物 (model organisms)

3.

動物發育的主要階段

4

發育過程之機制

4.

發育過程之機制

5.

組織再生與幹細胞