A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
29 10 2021
29 10 2021
Historique:
received:
20
03
2021
accepted:
01
10
2021
revised:
20
09
2021
entrez:
30
10
2021
pubmed:
31
10
2021
medline:
1
2
2022
Statut:
epublish
Résumé
While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA sequencing. The model generated astrocyte-specific gene expression patterns during differentiation that corresponded well to astroglia-specific expression signatures of in vivo cortical fetal development. Using this model we identified SCZ-specific expression dynamics, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology.
Identifiants
pubmed: 34716291
doi: 10.1038/s41398-021-01681-4
pii: 10.1038/s41398-021-01681-4
pmc: PMC8556332
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
554Informations de copyright
© 2021. The Author(s).
Références
Nat Neurosci. 1999 Feb;2(2):139-43
pubmed: 10195197
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Science. 1990 Jan 26;247(4941):470-3
pubmed: 1967852
J Exp Med. 2017 Dec 4;214(12):3481-3495
pubmed: 29141869
Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2675-84
pubmed: 27122314
Schizophr Res. 2009 Jul;112(1-3):54-64
pubmed: 19447584
Cell Rep. 2014 Jul 10;8(1):311-8
pubmed: 24981861
Arch Gen Psychiatry. 1995 Dec;52(12):1061-70
pubmed: 7492258
Bioinformatics. 2016 Oct 15;32(20):3201-3203
pubmed: 27354695
Front Psychiatry. 2018 Nov 06;9:544
pubmed: 30459650
Schizophr Bull. 2011 Jan;37(1):73-83
pubmed: 19443616
Nature. 2011 Oct 26;478(7370):483-9
pubmed: 22031440
Cell Transplant. 2012;21(8):1743-59
pubmed: 22490338
NPJ Schizophr. 2017 Apr 3;3:15
pubmed: 28560261
J Psychiatry Neurosci. 2014 Nov;39(6):376-85
pubmed: 24936776
Hum Genet. 2012 Mar;131(3):373-91
pubmed: 21866342
Lancet Psychiatry. 2020 Mar;7(3):272-281
pubmed: 31704113
Mol Psychiatry. 2009 Mar;14(3):252-60
pubmed: 19065143
Arch Gen Psychiatry. 2009 Sep;66(9):938-46
pubmed: 19736350
Transl Psychiatry. 2015 Aug 18;5:e623
pubmed: 26285133
Cell Rep. 2019 Jun 25;27(13):3832-3843.e6
pubmed: 31242417
Psychol Med. 1990 May;20(2):285-304
pubmed: 2356255
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18453-8
pubmed: 22027012
Epidemiol Rev. 2008;30:67-76
pubmed: 18480098
Stem Cell Res. 2018 Oct;32:25-34
pubmed: 30172094
Ther Targets Neurol Dis. 2014;1(1):
pubmed: 25590048
Matrix Biol. 2015 May-Jul;44-46:70-6
pubmed: 25622912
PLoS Biol. 2004 Apr;2(4):E96
pubmed: 15094801
Front Psychiatry. 2019 Jul 12;10:482
pubmed: 31354545
Hum Reprod. 2006 Aug;21(8):1990-9
pubmed: 16675485
Mol Psychiatry. 2020 Nov;25(11):2860-2872
pubmed: 30940904
Physiol Rev. 2009 Apr;89(2):411-52
pubmed: 19342611
Stem Cell Reports. 2017 Aug 8;9(2):615-628
pubmed: 28757163
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Biol Psychiatry. 2018 Dec 1;84(11):787-796
pubmed: 30177255
J Orthop Res. 2003 Mar;21(2):256-64
pubmed: 12568957
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
Schizophr Res. 2002 Oct 1;57(2-3):127-38
pubmed: 12223243
Neuropsychopharmacology. 2012 Jan;37(1):4-15
pubmed: 21956446
Trends Neurosci. 2015 Sep;38(9):535-49
pubmed: 26316036
Mol Psychiatry. 2014 Jan;19(1):20-9
pubmed: 24166406
Nature. 2010 Jan 14;463(7278):232-6
pubmed: 20075918
Psychiatry Res. 2001 Nov 30;108(2):65-78
pubmed: 11738541
Aust N Z J Psychiatry. 2014 Aug;48(8):722-34
pubmed: 24744400
Nat Rev Neurosci. 2010 Nov;11(11):735-46
pubmed: 20944663
Neuron. 2010 Mar 11;65(5):585-96
pubmed: 20223196
Brain Behav Immun. 2020 Jul;87:634-644
pubmed: 32109548
Cell Stem Cell. 2017 Aug 3;21(2):195-208.e6
pubmed: 28736215
J Neurosci. 2008 Jan 2;28(1):264-78
pubmed: 18171944
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Biol Psychiatry. 2018 Dec 1;84(11):778-786
pubmed: 29258653
Lancet Psychiatry. 2015 Mar;2(3):258-270
pubmed: 26359903
Br J Psychiatry. 2011 Mar;198(3):173-5
pubmed: 21357874
J Neurosci. 2017 Sep 6;37(36):8706-8717
pubmed: 28821665
Br J Psychiatry. 2002 Aug;181:138-43
pubmed: 12151285
Eur Arch Psychiatry Clin Neurosci. 2013 Feb;263(1):41-52
pubmed: 22660922
Neuron. 2014 Jul 2;83(1):69-86
pubmed: 24991955
Science. 2007 Aug 24;317(5841):1083-6
pubmed: 17717185
Mol Psychiatry. 2016 Sep;21(9):1167-79
pubmed: 27240529
Schizophr Bull. 2018 Oct 17;44(6):1195-1203
pubmed: 29762765
Brain Res. 2000 Dec 15;886(1-2):5-14
pubmed: 11119683
Nat Neurosci. 2016 Feb;19(2):182-9
pubmed: 26814587
Stem Cell Reports. 2018 Oct 9;11(4):897-911
pubmed: 30245212
Schizophr Bull. 2013 Jan;39(1):4-10
pubmed: 23172000
Stem Cell Reports. 2017 Aug 8;9(2):600-614
pubmed: 28757165
Psychol Med. 2019 Jul;49(10):1749-1757
pubmed: 30688187
Neuron. 2009 May 14;62(3):400-12
pubmed: 19447095
Genes Dev. 2012 May 1;26(9):891-907
pubmed: 22549954
Nat Genet. 2018 Mar;50(3):381-389
pubmed: 29483656
Proc Natl Acad Sci U S A. 2018 Oct 30;115(44):11316-11321
pubmed: 30327343
Biol Psychiatry. 1999 Jul 15;46(2):161-72
pubmed: 10418690
Bioinformatics. 2017 Mar 1;33(5):762-763
pubmed: 28011779
Front Pharmacol. 2020 Jan 29;10:1638
pubmed: 32063853
World Psychiatry. 2015 Jun;14(2):119-36
pubmed: 26043321
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Science. 1997 Feb 7;275(5301):844-7
pubmed: 9012354
J Psychiatr Res. 2016 Jan;72:43-50
pubmed: 26540403
Dev Neurobiol. 2011 Nov;71(11):956-81
pubmed: 21834084
Front Pharmacol. 2020 Feb 07;10:1612
pubmed: 32116664
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Nat Rev Neurosci. 2017 Dec;18(12):727-740
pubmed: 29070826
Arch Gen Psychiatry. 1990 Nov;47(11):1023-8
pubmed: 2241504
Nature. 2011 May 12;473(7346):221-5
pubmed: 21490598
Nature. 2009 Feb 5;457(7230):675-7
pubmed: 19194443
Neuron. 1992 Mar;8(3):429-40
pubmed: 1347996
Mol Cell Neurosci. 2007 Mar;34(3):310-23
pubmed: 17196394
J Neurosci. 2015 Mar 11;35(10):4427-39
pubmed: 25762685
Glia. 2015 Aug;63(8):1320-9
pubmed: 25963996
Mol Psychiatry. 2014 Jul;19(7):834-41
pubmed: 24419043
Neuropharmacology. 2012 Mar;62(3):1584-97
pubmed: 21856318
Biol Psychiatry. 2019 Apr 1;85(7):544-553
pubmed: 30340753