Mammary Epithelial Reconstitution With Gene-Modified Stem Cells

yourwish140

6 _7 y2 s, ^: O% G7 }7 \5 A0 ]! Y- V+ Y7 Q) g: c0 Q
The mammary gland represents a unique model. q, d0 J" h, T" m# J; o
system to study gene functions in adult stem cells.8 ~- g0 y- e- q# X3 T+ C  ?; p2 ]% D
Mammary stem cells (MaSCs) can regenerate a. I6 g& c, Y' S! |! e0 d
functional epithelium upon transplantation into' K, F3 i5 ?! e- K& s
cleared fat pads. We studied the consequences of8 }+ t9 u' f8 I% \  c! K
distinct genetic modifications of MaSCs on their
2 E8 M; T) A# w3 Urepopulation and differentiation ability. The
% [5 I7 k+ G3 I+ B2 G! R4 ?( D! M! X: Mreconstitution of ductal trees was used as a stem cell
6 i2 d& l, g- b! b+ _selection procedure and the nearly quantitative5 I/ {6 G% o2 @+ L7 T% z
lentiviral infection efficiency of the primary9 W$ m% Q- L+ \* J9 M( J8 g& P7 y
mammary epithelial cells (MECs) rendered the8 O* B) }# `! o& o
enrichment of MaSCs prior to their transplantation# t6 N9 N7 D7 g3 X! U+ z+ v. r9 ~
unnecessary. The repopulation frequency of
1 p$ k/ m# g- I7 }# ]) n+ h- |transduced MaSCs was nearly 100% in
/ u9 B4 a! O6 l. G9 A* A* m, }immunodeficient recipients and the resulting
) o$ B3 G( G3 m* utransgenic ducts homogeneously expressed the virally% U4 ^, R  p1 m8 E. @! e
encoded fluorescent marker proteins.
# O4 b4 A+ F3 q3 I% [Transplantation of a mixture of MECs, expressing( h! T* ^+ G0 W  ^# ?. K
different fluorescent proteins, resulted in a distinct3 c0 l* H5 w/ C- |  A8 t3 h  X
pattern of ductal outgrowths originating from a small
) X1 U. s/ ~8 j4 Gnumber of individually transduced MaSCs. We used1 ^3 i, h3 b1 }+ `" k
genetically modified MECs to define multiple
- C; N( ?% X& \9 }4 cfunctions of Stat5 during mammary gland/ {0 ^& ^3 J  |' {
development and differentiation. Stat5-6 B5 R  j4 g9 t+ o: |, A2 S& L
downregulation in MaSCs did not affect primary. x8 q& |4 p! _- I. Y- R; n+ I
ductal outgrowth, but impaired side-branching and
' Q) H, k$ o( ^4 [/ pthe emergence of mature alveolar cells from luminal
- _6 y1 r  W4 e# {, [progenitors during pregnancy. Conversely, the  v% J" L( J: j! M; P3 b. `
expression of a constitutively active variant of Stat5,' \1 X  j5 t+ v1 |, Z
cS5-F, caused epithelial hyperproliferation,# B: e. N4 [3 H7 u" X( _( H/ ?( n
thickening of the ducts and precocious, functional
4 Q+ y2 W9 z( S% D: balveoli formation in virgin mice. Expression of cS5-F4 @0 D; I- `# J# B( ^
also prevented involution and caused the formation2 _) Z8 \8 q) e. v: d
of ER+PR+ adenocarcinomas. The tumors expressed8 G* Q" M+ p' L  y. S3 k
activated Stat5 and Stat3 and contained a small% c! S* `8 y6 e  _: Y/ N. p
fraction of CD44+ cells, possibly indicative of cancer
% V9 L# Z6 w& G: H. i7 Y5 P6 Estem cells (CSCs)

tuanzi

其实回帖算是一种没德德，所以我快成圣人了  

剑啸寒

也许似乎大概是，然而未必不见得。  

nauticus

说的真有道理啊！

txxxtyq

楼主福如东海，万寿无疆！  

大小年

我来看看！谢谢  

橙味绿茶

支持一下  

我心飞翔

声明一下：本人看贴和回贴的规则，好贴必看，精华贴必回。  

陈晴

一个有信念者所开发出的力量，大于99个只有兴趣者。  

marysyq

活着，以死的姿态……