A mesenchymal-like ZEB1(+) niche harbors dorsal radial glial fibrillary acidic protein-positive stem cells in the spinal cord.
In humans and rodents the adult spinal cord harbors neural stem cells located around the central canal. Their identity, precise location, and specific signaling are still ill-defined and controversial. We report here on a detailed analysis of this niche. Using microdissection and glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP) transgenic mice, we demonstrate that neural stem cells are mostly dorsally located GFAP(+) cells lying ependymally and subependymally that extend radial processes toward the pial surface. The niche also harbors doublecortin protein (Dcx)(+) Nkx6.1(+) neurons sending processes into the lumen. Cervical and lumbar spinal cord neural stem cells maintain expression of specific rostro-caudal Hox gene combinations and the niche shows high levels of signaling proteins (CD15, Jagged1, Hes1, differential screening-selected gene aberrative in neuroblastoma [DAN]). More surprisingly, the niche displays mesenchymal traits such as expression of epithelial-mesenchymal-transition zinc finger E-box-binding protein 1 (ZEB1) transcription factor and smooth muscle actin. We found ZEB1 to be essential for neural stem cell survival in vitro. Proliferation within the niche progressively ceases around 13 weeks when the spinal cord reaches its final size, suggesting an active role in postnatal development. In addition to hippocampus and subventricular zone niches, adult spinal cord constitutes a third central nervous system stem cell niche with specific signaling, cellular, and structural characteristics that could possibly be manipulated to alleviate spinal cord traumatic and degenerative diseases.
Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France.
Jean-Charles
JC
Sabourin
Karin B
KB
Ackema
David
D
Ohayon
Pierre-Olivier
PO
Guichet
Florence E
FE
Perrin
Alain
A
Garces
Chantal
C
Ripoll
Jeroen
J
Charité
Lionel
L
Simonneau
H
H
Kettenmann
Azel
A
Zine
Alain
A
Privat
Jean
J
Valmier
Alexandre
A
Pattyn
Jean-Philippe
JP
Hugnot
D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D000089662:Doublecortin Protein; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism*; D055153:Stem Cell Niche / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
D000199:Actins; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D049452:Green Fluorescent Proteins