Highly efficient generation of glutamatergic/cholinergic NT2-derived postmitotic human neurons by short-term treatment with the nucleoside analogue cytosine β-d-arabinofuranoside

The human NTERA2/D1 (NT2) cells generate postmitotic neurons (NT2N cells) upon retinoic acid (RA) treatment and are functionally integrated in the host tissue following grafting into the rodent and human brain, thus representing a promising source for neuronal replacement therapy. Yet the major limi...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Stem cell research Ročník 16; číslo 2; s. 541 - 551
Hlavní autoři:	González-Burguera, Imanol, Ricobaraza, Ana, Aretxabala, Xabier, Barrondo, Sergio, García del Caño, Gontzal, López de Jesús, Maider, Sallés, Joan
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier B.V 01.03.2016 Elsevier
Témata:	Animals Blotting, Western Brain - metabolism Cell Differentiation - drug effects Cell Line, Tumor Cell Proliferation - drug effects Choline O-Acetyltransferase - metabolism Cholinergic Neurons - cytology Cholinergic Neurons - drug effects Cholinergic Neurons - metabolism Cytarabine - pharmacology Cytosine β-d-arabinofuranoside Glutamate Decarboxylase - metabolism Humans Microscopy, Fluorescence Neurogenesis - drug effects Neuronal differentiation Neurotransmitter phenotype Pluripotent NT2 cells Postmitotic human neurons Rats Retinoic acid Tyrosine 3-Monooxygenase - metabolism Vesicular Glutamate Transport Protein 1 - metabolism Neuronal differentiation Postmitotic human neurons Cytosine β-d-arabinofuranoside Pluripotent NT2 cells Retinoic acid Neurotransmitter phenotype
ISSN:	1873-5061, 1876-7753, 1876-7753
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	The human NTERA2/D1 (NT2) cells generate postmitotic neurons (NT2N cells) upon retinoic acid (RA) treatment and are functionally integrated in the host tissue following grafting into the rodent and human brain, thus representing a promising source for neuronal replacement therapy. Yet the major limitations of this model are the lengthy differentiation procedure and its low efficiency, although recent studies suggest that the differentiation process can be shortened to less than 1week using nucleoside analogues. To explore whether short-term exposure of NT2 cells to the nucleoside analogue cytosine β-d-arabinofuranoside (AraC) could be a suitable method to efficiently generate mature neurons, we conducted a neurochemical and morphometric characterization of AraC-differentiated NT2N (AraC/NT2N) neurons and improved the differentiation efficiency by modifying the cell culture schedule. Moreover, we analyzed the neurotransmitter phenotypes of AraC/NT2N neurons. Cultures obtained by treatment with AraC were highly enriched in postmitotic neurons and essentially composed of dual glutamatergic/cholinergic neurons, which contrasts with the preferential GABAergic phenotype that we found after RA differentiation. Taken together, our results further reinforce the notion NT2 cells are a versatile source of neuronal phenotypes and provide a new encouraging platform for studying mechanisms of neuronal differentiation and for exploring neuronal replacement strategies. [Display omitted] •NT2 cells differentiate into human postmitotic neurons by short-term treatment with AraC.•Increase in confluence at mid-point of AraC treatment yielded higher differentiation efficiency.•AraC-differentiated neurons display a dual glutamatergic/cholinergic phenotype.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1873-5061 1876-7753 1876-7753
DOI:	10.1016/j.scr.2016.02.038