Wnt-mediated self-renewal of neural stem/progenitor cells

被引：258

作者：

Kalani, M. Yashar S. ^{[1
,2
,5
]}

Cheshier, Samuel H. ^{[3
,5
]}

Cord, Branden J. ^{[3
]}

Bababeygy, Simon R. ^{[1
]}

Vogel, Hannes ^{[4
]}

Weissman, Irving L. ^{[1
,3
,4
,5
]}

Palmer, Theo D. ^{[3
]}

Nusse, Roel ^{[1
,2
,5
]}

机构：

[1] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 44期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1073/pnas.0808616105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In this work we have uncovered a role for Writ signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells in the subventricular zone of the developing E14.5 mouse brain. Responding cell populations were enriched for self-renewing stem cells in primary culture, suggesting that Wnt signaling is a hallmark of self-renewing activity in vivo. We also tested whether Writ signals directly influence neural stem cells. Using inhibitors of the Writ pathway, we found that Writ signaling is required for the efficient cloning and expansion of single-cell derived populations that are able to generate new stem cells as well as neurons, astrocytes, and oligodendrocytes. The addition of exogenous Wnt3a protein enhances clonal outgrowth, demonstrating not only a critical role for the Writ pathway for the regulation of neurogenesis but also its use for the expansion of neural stem cells in cell culture and in tissue engineering.

引用

页码：16970 / 16975

页数：6

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