In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells.
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 prominin1 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 prominin1 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.
Institute for Stem Cell Research, Helmholtz Centre Munich German Research Centre for Environmental Health, Neuherberg/Munich, Germany.
Ruth
R
Beckervordersandforth
Pratibha
P
Tripathi
Jovica
J
Ninkovic
Efil
E
Bayam
Alexandra
A
Lepier
Barbara
B
Stempfhuber
Frank
F
Kirchhoff
Johannes
J
Hirrlinger
Anja
A
Haslinger
D Chichung
DC
Lie
Johannes
J
Beckers
Bradley
B
Yoder
Martin
M
Irmler
Magdalena
M
Götz
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; C098623:IFT88 protein, human; D025521:Tumor Suppressor Proteins