Cell reports：Notch 和 Wnt调节小肠干细胞分化平衡新机制（附原文）

defu

9 c+ R- K5 E: U7 B

6 O' B% s6 K8 W1 X6 |( L: [5 Y# w来源：生物谷 2015-03-30 11:02
4 K6 D6 I" O/ x1 x2 \$ I
( H$ }4 W# \! [" a* `0 E- w: \- p$ S( j5 A$ Q" @, S4 P
' z2 E1 B  f. m$ M8 ^7 a
2015年3月30日讯 /生物谷BIOON/ --近日，国际学术期刊cell reports在线发表了美国科学家的一项最新研究进展，他们发现在小肠干细胞和小肠稳态调节过程中，Notch和Wnt信号扮演了重要调控作用，阻断Notch信号会引起小肠干细胞分化失衡，并且在这一过程中伴随对Wnt信号途径的抑制解除。
# Q; b2 W( Q8 X6 q4 s1 _4 K : }6 ^$ l/ [1 O. |; V; |
' M* q8 \* U/ r9 x

  g! e4 Q. R1 T4 P4 h2 v器官的稳态平衡需要对成体干细胞进行严格调控，并通过多种信号整合实现干细胞向终末细胞的分化过程。在小鼠的小肠中，Notch和wnt信号对于小肠干细胞维持以及肠道负责消化液分泌的细胞和负责营养吸收的细胞之间的分化平衡都是非常必要的。
( `$ |5 N. Q8 }0 n, G 3 Q) B+ S3 a! D! W6 [2 P: \. n

9 {( F4 ~( g* o" d8 W6 s: \
$ k& @3 x, `, ?# ?; w" m研究人员发现当Notch信号受到抑制，小肠干细胞倾向于向分泌细胞方向分化，而影响营养吸收细胞的分化过程。研究人员利用具有功能阻断特性的抗体特异性阻断Notch受体，结果发现阻断Notch信号会解除对Wnt信号途径的抑制作用，扰乱小肠干细胞的正常功能，导致促分泌功能相关基因的错误表达。同时，研究人员还发现抑制wnt信号通路能够恢复因Notch信号阻断所造成的表型。  a! P; E3 U# Q" c3 q0 e

: M! [& \* N5 g. I# X' _ " D" S& a- L1 a/ ^

6 x* @% O$ X( f. N这项研究阐述了一种维持干细胞活性以及分化平衡的负向调节机制，并且还证明了Wnt与Notch信号之间的相互作用对与维持成体干细胞的正常功能具有重要意义。
' D0 d' Z% O2 Q
8 ~9 c+ v6 S: ?( f2 ?3楼原文 感谢WeiTing 提供

defu

( O, W& u, ^" {+ E, w+ I 7 U) v) f. S8 N9 i3 f4 S

! T, ]9 r3 Z; `4 R7 l; @; f3 Q
6 `. V; h# y" U2 V6 C . Z/ R- E9 F$ d2 g$ ~4 s
# G$ M2 y7 _0 n' B2 C* J
DOI: http://dx.doi.org/10.1016/j.celrep.2015.03.007
( H& m2 V# K2 Q: w
" e- X7 ^4 C5 P+ D7 e 9 j% c. h$ Z  K# A

) j, `2 X& B0 p; j
" ~1 g  i) R+ T7 ?Opposing Activities of Notch and Wnt Signaling Regulate Intestinal Stem Cells and Gut Homeostasis/ w5 ]" K3 K* E3 Q. o# H: M
* H: {$ B7 s# K- B; e
9 t- L  B& z  j7 T

+ q* {/ [, a% i1 s3 Z4 g& q! ]1 C( uHua Tian5, Brian Biehs5, Cecilia Chiu, Christian W. Siebel, Yan Wu, Mike Costa, Frederic J. de Sauvagecorrespondenceemail, Ophir D. Klein$ u4 f' C6 h5 `
& Q  [& O% w! @( Q$ z

: b  `3 m$ n- @- P) f7 |( ^  @
9 ]$ n5 u6 U; G% w% X0 mProper organ homeostasis requires tight control of adult stem cells and differentiation through the integration of multiple inputs. In the mouse small intestine, Notch and Wnt signaling are required both for stem cell maintenance and for a proper balance of differentiation between secretory and absorptive cell lineages. In the absence of Notch signaling, stem cells preferentially generate secretory cells at the expense of absorptive cells. Here, we use function-blocking antibodies against Notch receptors to demonstrate that Notch blockade perturbs intestinal stem cell function by causing a derepression of the Wnt signaling pathway, leading to misexpression of prosecretory genes. Importantly, attenuation of the Wnt pathway rescued the phenotype associated with Notch blockade. These studies bring to light a negative regulatory mechanism that maintains stem cell activity and balanced differentiation, and we propose that the interaction between Wnt and Notch signaling described here represents a common theme in adult stem cell biology.

WeiTing

回复 defu 的帖子7 J8 d( c% ?+ u- Y& W0 u- q
0 o$ c% c' ?3 o6 m, Q
Opposing Activities of Notch and Wnt Signaling Regulate Intestinal Stem Cells and Gut Homeostasis