Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments.
Neural stem (NS) cells are a self-renewing population of symmetrically dividing multipotent radial glia-like stem cells, characterized by homogeneous expansion in monolayer. Here we report that fetal NS cells isolated from different regions of the developing mouse nervous system behave in a similar manner with respect to self-renewal and neuropotency, but exhibit distinct positional identities. For example, NS cells from the neocortex maintain the expression of anterior transcription factors, including Otx2 and Foxg1, while Hoxb4 and Hoxb9 are uniquely found in spinal cord-derived NS cells. This molecular signature was stable for over 20 passages and was strictly linked to the developmental stage of the donor, because only NS cells derived from E14.5 cortex, and not those derived from E12.5 cortex, carried a consistent transcription factor profile. We also showed that traits of this positional code are maintained during neuronal differentiation, leading to the generation of electrophysiologically active neurons, even if they do not acquire a complete neurochemical identity.
Onorati
Marco
M
Department of Pharmacological Sciences and Center for Stem Cell Research, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
Binetti
Maurizio
M
Conti
Luciano
L
Camnasio
Stefano
S
Calabrese
Giovanna
G
Albieri
Ilaria
I
Di Febo
Francesca
F
Toselli
Mauro
M
Biella
Gerardo
G
Martynoga
Ben
B
Guillemot
Francois
F
Consalez
G Giacomo
GG
Cattaneo
Elena
E
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019579:Neocortex / Q000166:cytology / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism*; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; C104161:Hoxb9 protein, mouse; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D014157:Transcription Factors