All-trans retinoic acid induces reprogramming of canine dedifferentiated cells into neuron-like cells.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
04
11
2019
accepted:
16
02
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
19
6
2020
Statut:
epublish
Résumé
The specification of cell identity depends on the exposure of cells to sequences of bioactive ligands. All-trans retinoic acid (ATRA) affects neuronal development in the early stage, and it is involved in neuronal lineage reprogramming. We previously established a fibroblast-like dedifferentiated fat cells (DFATs) derived from highly homogeneous mature adipocytes, which are more suitable for the study of cellular reprogramming. Canine cognitive dysfunction is similar to human cognitive dysfunction, suggesting that dogs could be a pathological and pharmacological model for human neuronal diseases. However, the effect of ATRA on neuronal reprogramming in dogs has remained unclear. Therefore, in this study, we investigated the effect of ATRA on the neuronal reprogramming of canine DFATs. ATRA induced the expression of neuronal marker mRNA/protein. The neuron-like cells showed Ca2+ influx with depolarization (50 mM KCl; 84.75 ± 4.05%) and Na+ channel activation (50 μM veratridine; 96.02 ± 2.02%). Optical imaging of presynaptic terminal activity and detection of neurotransmitter release showed that the neuron-like cells exhibited the GABAergic neuronal property. Genome-wide RNA-sequencing analysis shows that the transcriptome profile of canine DFATs is effectively reprogrammed towards that of cortical interneuron lineage. Collectively, ATRA can produce functional GABAergic cortical interneuron-like cells from canine DFATs, exhibiting neuronal function with > 80% efficiency. We further demonstrated the contribution of JNK3 to ATRA-induced neuronal reprogramming in canine DFATs. In conclusion, the neuron-like cells from canine DFATs could be a powerful tool for translational research in cell transplantation therapy, in vitro disease modeling, and drug screening for neuronal diseases.
Identifiants
pubmed: 32231396
doi: 10.1371/journal.pone.0229892
pii: PONE-D-19-30780
pmc: PMC7108708
doi:
Substances chimiques
RNA, Messenger
0
Tretinoin
5688UTC01R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0229892Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Biochim Biophys Acta. 2007 Aug;1773(8):1341-8
pubmed: 17306896
J Neurosci. 2007 Nov 21;27(47):12787-96
pubmed: 18032650
Stem Cell Reports. 2017 Aug 8;9(2):557-570
pubmed: 28793248
PLoS One. 2018 Dec 18;13(12):e0208955
pubmed: 30562372
Vet J. 2011 Jun;188(3):331-6
pubmed: 20542455
Stem Cells. 2014 Jul;32(7):1789-804
pubmed: 24648391
Int J Mol Sci. 2017 Dec 13;18(12):
pubmed: 29236047
Exp Brain Res. 2010 Jan;200(2):161-7
pubmed: 19621217
Am J Vet Res. 2013 Oct;74(10):1311-20
pubmed: 24066915
Nat Protoc. 2013 Sep;8(9):1670-9
pubmed: 23928500
Genes Dev. 1990 Jun;4(6):932-42
pubmed: 2384214
Mol Cell Neurosci. 2007 Oct;36(2):248-59
pubmed: 17728141
PLoS One. 2015 Nov 02;10(11):e0141581
pubmed: 26523832
PLoS Biol. 2011 Apr;9(4):e1000609
pubmed: 21532733
J Endod. 2012 Oct;38(10):1355-62
pubmed: 22980177
Nat Rev Neurosci. 2007 Oct;8(10):755-65
pubmed: 17882253
Organogenesis. 2016 Jul 2;12(3):119-127
pubmed: 27322672
Nat Commun. 2014 Feb 26;5:3368
pubmed: 24569594
Cell Tissue Res. 2008 Jun;332(3):435-46
pubmed: 18386066
Anal Biochem. 1976 May 7;72:248-54
pubmed: 942051
Cell Stem Cell. 2015 Dec 3;17(6):735-747
pubmed: 26481520
Biochem Biophys Res Commun. 2011 Apr 15;407(3):562-7
pubmed: 21419102
PLoS One. 2011;6(5):e19768
pubmed: 21611190
Alzheimers Res Ther. 2014 Jul 03;6(4):37
pubmed: 25024750
Development. 1992 Jun;115(2):487-501
pubmed: 1358593
Microbiol Mol Biol Rev. 2006 Dec;70(4):1061-95
pubmed: 17158707
Cell Stem Cell. 2015 Aug 6;17(2):195-203
pubmed: 26253201
Nat Rev Neurosci. 2004 Oct;5(10):793-807
pubmed: 15378039
Vet Immunol Immunopathol. 2015 Dec 15;168(3-4):223-32
pubmed: 26549149
Differentiation. 2010 Jul;80(1):20-30
pubmed: 20427117
Front Neural Circuits. 2016 Aug 17;10:64
pubmed: 27582692
PLoS One. 2019 Jul 25;14(7):e0220262
pubmed: 31344106
Eur J Neurosci. 2008 Sep;28(5):883-92
pubmed: 18717734
J Cell Physiol. 2008 Apr;215(1):210-22
pubmed: 18064604
Sci Rep. 2018 Jun 4;8(1):8535
pubmed: 29867151
PLoS One. 2019 Sep 19;14(9):e0222869
pubmed: 31536594
Cell Stem Cell. 2013 May 2;12(5):573-86
pubmed: 23642366
Neurobiol Aging. 1996 Mar-Apr;17(2):259-68
pubmed: 8744407
PLoS One. 2016 Nov 16;11(11):e0166707
pubmed: 27851800
Nature. 1992 Dec 24-31;360(6406):737-41
pubmed: 1361214
Stem Cell Reports. 2017 Mar 14;8(3):538-547
pubmed: 28216149
CNS Drugs. 2009 Nov;23(11):915-26
pubmed: 19845413
Cell Stem Cell. 2015 Aug 6;17(2):204-12
pubmed: 26253202
Development. 1997 Jan;124(2):373-9
pubmed: 9053313
Vet J. 2014 Jan;199(1):88-96
pubmed: 24300011
Cell Stem Cell. 2016 May 5;18(5):653-67
pubmed: 27133794
Development. 2004 Jun;131(11):2653-67
pubmed: 15128657
Cell Stem Cell. 2013 May 2;12(5):559-72
pubmed: 23642365
Stem Cells. 2011 Mar;29(3):462-73
pubmed: 21425409
Stem Cells. 2011 May;29(5):802-11
pubmed: 21381151
J Vet Med Sci. 2015 Jan;77(1):27-35
pubmed: 25284120
PLoS One. 2017 Aug 14;12(8):e0182923
pubmed: 28806729
Sci Rep. 2017 Jan 05;7:39914
pubmed: 28054591
Cell. 1991 Oct 4;67(1):89-104
pubmed: 1680565