SOX9-induced Generation of Functional Astrocytes Supporting Neuronal Maturation in an All-human System.
All-human co-culture system
Astrocytes
Differentiation protocol
Genome engineering
Pluripotent stem cells
Journal
Stem cell reviews and reports
ISSN: 2629-3277
Titre abrégé: Stem Cell Rev Rep
Pays: United States
ID NLM: 101752767
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
accepted:
29
04
2021
pubmed:
14
5
2021
medline:
8
3
2022
entrez:
13
5
2021
Statut:
ppublish
Résumé
Astrocytes, the main supportive cell type of the brain, show functional impairments upon ageing and in a broad spectrum of neurological disorders. Limited access to human astroglia for pre-clinical studies has been a major bottleneck delaying our understanding of their role in brain health and disease. We demonstrate here that functionally mature human astrocytes can be generated by SOX9 overexpression for 6 days in pluripotent stem cell (PSC)-derived neural progenitor cells. Inducible (i)SOX9-astrocytes display functional properties comparable to primary human astrocytes comprising glutamate uptake, induced calcium responses and cytokine/growth factor secretion. Importantly, electrophysiological properties of iNGN2-neurons co-cultured with iSOX9-astrocytes are indistinguishable from gold-standard murine primary cultures. The high yield, fast timing and the possibility to cryopreserve iSOX9-astrocytes without losing functional properties makes them suitable for scaled-up production for high-throughput analyses. Our findings represent a step forward to an all-human iPSC-derived neural model for drug development in neuroscience and towards the reduction of animal use in biomedical research.
Identifiants
pubmed: 33982246
doi: 10.1007/s12015-021-10179-x
pii: 10.1007/s12015-021-10179-x
pmc: PMC8553725
doi:
Substances chimiques
SOX9 Transcription Factor
0
SOX9 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1855-1873Informations de copyright
© 2021. The Author(s).
Références
EMBO Rep. 2018 Nov;19(11):
pubmed: 30166336
Stem Cell Reports. 2017 Dec 12;9(6):1885-1897
pubmed: 29153989
Nat Biotechnol. 2019 Mar;37(3):267-275
pubmed: 30804533
Neuron. 2017 Aug 16;95(4):779-790.e6
pubmed: 28817799
Trends Neurosci. 1997 Dec;20(12):570-7
pubmed: 9416670
Exp Neurol. 2018 Nov;309:23-31
pubmed: 30044944
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Alzheimers Dement. 2018 Oct;14(10):1261-1280
pubmed: 30036493
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4148-53
pubmed: 11259680
J Mass Spectrom. 1996 Mar;31(3):255-62
pubmed: 8799277
Brain Struct Funct. 2017 Jul;222(5):2017-2029
pubmed: 28280934
PLoS One. 2013 Nov 07;8(11):e80574
pubmed: 24348912
Sci Rep. 2016 Nov 07;6:36529
pubmed: 27819315
BMC Bioinformatics. 2011 Dec 17;12:480
pubmed: 22177264
Neuroscience. 1996 Apr;71(3):871-83
pubmed: 8867055
Methods. 2016 May 15;101:113-24
pubmed: 26626326
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Neuron. 2008 Sep 25;59(6):932-46
pubmed: 18817732
Nat Commun. 2017 May 11;8:15267
pubmed: 28492237
Genes Dev. 2003 Jul 1;17(13):1677-89
pubmed: 12842915
Brain Res Rev. 2010 May;63(1-2):39-46
pubmed: 19931561
Cells. 2019 Feb 20;8(2):
pubmed: 30791579
Nat Methods. 2018 Sep;15(9):693-696
pubmed: 30127505
Methods Mol Biol. 2019;1862:53-66
pubmed: 30315459
Stem Cells Transl Med. 2019 Dec;8(12):1272-1285
pubmed: 31631575
J Cell Sci. 2019 Feb 1;132(3):
pubmed: 30617110
Prog Neurobiol. 2008 Dec 11;86(4):342-67
pubmed: 18948166
Stem Cell Reports. 2018 Feb 13;10(2):655-672
pubmed: 29337119
Nat Protoc. 2020 Nov;15(11):3716-3744
pubmed: 33097924
Neuron. 2013 Jun 5;78(5):785-98
pubmed: 23764284
Brain Pathol. 2018 May;28(3):372-387
pubmed: 29740942
Glia. 2008 May;56(7):734-49
pubmed: 18293404
Stem Cells. 2013 Apr;31(4):741-51
pubmed: 23307615
Stem Cell Reports. 2020 Jul 14;15(1):38-51
pubmed: 32502466
Front Mol Neurosci. 2017 Dec 19;10:427
pubmed: 29311817
Stem Cell Reports. 2019 Feb 12;12(2):213-229
pubmed: 30639209
Nat Commun. 2017 Oct 11;8(1):861
pubmed: 29021520
Acta Neuropathol Commun. 2018 Aug 8;6(1):74
pubmed: 30089511
J Neurosci. 2009 Mar 11;29(10):3276-87
pubmed: 19279265
Bioinformatics. 2007 Nov 1;23(21):2881-7
pubmed: 17881408
Neuron. 2016 Jan 6;89(1):37-53
pubmed: 26687838
Neurochem Res. 2013 Jun;38(6):1260-5
pubmed: 23519933
Cell Rep. 2019 May 14;27(7):2199-2211.e6
pubmed: 31091456
Bioinformatics. 2009 Oct 1;25(19):2607-8
pubmed: 19654119
Front Aging Neurosci. 2018 Oct 26;10:337
pubmed: 30416441
Neuron. 2020 Aug 5;107(3):436-453.e12
pubmed: 32485136
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Stem Cell Reports. 2019 Feb 12;12(2):201-212
pubmed: 30639213
Stem Cell Reports. 2018 Nov 13;11(5):1199-1210
pubmed: 30409508
Sci Rep. 2019 Nov 15;9(1):16944
pubmed: 31729450
J Neurosci. 2015 Nov 11;35(45):15199-213
pubmed: 26558789
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Stem Cell Reports. 2015 Jan 13;4(1):25-36
pubmed: 25556566
Biomaterials. 2015 Feb;42:134-43
pubmed: 25542801
Nat Rev Neurosci. 2018 Jul;19(7):393-403
pubmed: 29777182
Stem Cell Reports. 2015 Nov 10;5(5):918-931
pubmed: 26455413
Metab Eng. 2017 Sep;43(Pt B):187-197
pubmed: 27847310
Stem Cell Reports. 2018 Oct 9;11(4):998-1008
pubmed: 30269954
Front Endocrinol (Lausanne). 2013 Aug 15;4:102
pubmed: 23966981