In Vivo Fate Mapping and Expression Analysis Reveals Molecular Hallmarks of Prospectively Isolated Adult Neural Stem Cells

被引：262

作者：

Beckervordersandforth, Ruth ^{[1
]}

Tripathi, Pratibha ^{[1
]}

Ninkovic, Jovica ^{[1
,4
]}

Bayam, Efil ^{[1
]}

Lepier, Alexandra ^{[4
]}

Stempfhuber, Barbara ^{[1
]}

Kirchhoff, Frank ^{[5
,6
]}

Hirrlinger, Johannes ^{[7
]}

Haslinger, Anja ^{[2
]}

Lie, D. Chichung ^{[2
]}

Beckers, Johannes ^{[3
,8
]}

Yoder, Bradley ^{[9
]}

Irmler, Martin ^{[3
]}

Goetz, Magdalena ^{[1
,4
]}

机构：

[1] German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Inst Stem Cell Res, D-85764 Neuherberg, Germany

[2] German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Res Grp Adult Neural Stem Cells & Neurogenesis, Inst Dev Genet, D-85764 Neuherberg, Germany

[3] German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Inst Expt Genet, D-85764 Neuherberg, Germany

[4] Univ Munich, Fac Med, D-80633 Munich, Germany

[5] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany

[6] DFG Res Ctr Mol Physiol Brain, D-37075 Gottingen, Germany

[7] Univ Leipzig, Fac Med, Carl Ludwig Inst Physiol & Neural Plast N05, D-04103 Leipzig, Germany

[8] Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, D-85354 Freising Weihenstephan, Germany

[9] Univ Birmingham, Birmingham, AL 35294 USA

来源：

CELL STEM CELL | 2010年 / 7卷 / 06期

关键词：

SUBVENTRICULAR ZONE ASTROCYTES; EPENDYMAL CELLS; PRIMARY CILIA; RADIAL GLIA; GENE; MICE; DIFFERENTIATION; TRANSCRIPTOME; PROLIFERATION; SPECIFICATION;

D O I：

10.1016/j.stem.2010.11.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Until now, limitations in the ability to enrich adult NSCs (aNSCs) have hampered meaningful analysis of these cells at the transcriptome level. Here we show via a split-Cre technology that coincident activity of the hGFAP and promininl promoters is a hallmark of aNSCs in vivo. Sorting of cells from the adult mouse subependymal zone (SEZ) based on their expression of GFAP and promininl isolates all self-renewing, multipotent stem cells at high purity. Comparison of the transcriptome of these purified aNSCs to parenchymal nonneurogenic astrocytes and other SEZ cells reveals aNSC hallmarks, including neuronal lineage priming and the importance of cilia- and Ca-dependent signaling pathways. Inducible deletion of the ciliary protein IFT88 in aNSCs validates the role of ciliary function in aNSCs. Our work reveals candidate molecular regulators for unique features of aNSCs and facilitates future selective analysis of aNSCs in other functional contexts, such as aging and injury.

引用

页码：744 / 758

页数：15

共 52 条

[1] Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression [J].

Basak, Onur ;

Taylor, Verdon .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2007, 25 (04) :1006-1022

[2] The establishment of neuronal properties is controlled by Sox4 and Sox11 [J].

Bergsland, Maria ;

Werme, Martin ;

Malewicz, Michal ;

Perlmann, Thomas ;

Muhr, Jonas .

GENES & DEVELOPMENT, 2006, 20 (24) :3475-3486

[3] Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling [J].

Breunig, Joshua J. ;

Sarkisian, Matthew R. ;

Arellano, Jon I. ;

Morozov, Yury M. ;

Ayoub, Albert E. ;

Sojitra, Sonal ;

Wang, Baolin ;

Flavell, Richard A. ;

Rakic, Pasko ;

Town, Terrence .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (35) :13127-13132

[4] A Dlx2-and Pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb [J].

Brill, Monika S. ;

Snapyan, Marina ;

Wohlfrom, Hilde ;

Ninkovic, Jovica ;

Jawerka, Melanie ;

Mastick, Grant S. ;

Ashery-Padan, Ruth ;

Saghatelyan, Armen ;

Berninger, Benedikt ;

Goetz, Magdalena .

JOURNAL OF NEUROSCIENCE, 2008, 28 (25) :6439-6452

[5] Origin and progeny of reactive gliosis:: A source of multipotent cells in the injured brain [J].

Buffo, Annalisa ;

Rite, Inmaculada ;

Tripathi, Pratibha ;

Lepier, Alexandra ;

Colak, Dilek ;

Horn, Ana-Paula ;

Mori, Tetsuji ;

Goetz, Magdalena .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (09) :3581-3586

[6] LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal [J].

Capela, A ;

Temple, S .

NEURON, 2002, 35 (05) :865-875

[7] Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke [J].

Carlen, Marie ;

Meletis, Konstantinos ;

Goritz, Christian ;

Darsalia, Vladimer ;

Evergren, Emma ;

Tanigaki, Kenji ;

Amendola, Mario ;

Barnabe-Heider, Fanie ;

Yeung, Maggie S. Y. ;

Naldini, Luigi ;

Honjo, Tasuku ;

Kokaia, Zaal ;

Shupliakov, Oleg ;

Cassidy, Robert M. ;

Lindvall, Olle ;

Frisen, Jonas .

NATURE NEUROSCIENCE, 2009, 12 (03) :259-267

[8] Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion [J].

Chitaev, NA ;

Troyanovsky, SM .

JOURNAL OF CELL BIOLOGY, 1997, 138 (01) :193-201

[9] Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? [J].

Chojnacki, Andrew K. ;

Mak, Gloria K. ;

Weiss, Samuel .

NATURE REVIEWS NEUROSCIENCE, 2009, 10 (02) :153-163

[10] Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR [J].

Ciccolini, F ;

Mandl, C ;

Hölzl-Wenig, G ;

Kehlenbach, A ;

Hellwig, A .

DEVELOPMENTAL BIOLOGY, 2005, 284 (01) :112-125

← 1 2 3 4 5 6 →