A single-cell transcriptome atlas of the adult human retina.
Autopsy
Cluster Analysis
Databases, Genetic
Gene Expression Profiling
/ methods
Gene Expression Regulation
Humans
Nerve Degeneration
/ genetics
Organ Specificity
RNA, Long Noncoding
/ genetics
Retina
/ chemistry
Retinal Rod Photoreceptor Cells
/ chemistry
Sequence Analysis, RNA
Single-Cell Analysis
/ methods
Transcriptome
Unsupervised Machine Learning
photoreceptor subtypes
retina
single-cell RNA sequencing
transcriptome
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
16 09 2019
16 09 2019
Historique:
received:
28
09
2018
revised:
29
07
2019
accepted:
31
07
2019
pubmed:
23
8
2019
medline:
27
12
2019
entrez:
23
8
2019
Statut:
ppublish
Résumé
The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single-cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post-mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell-derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.
Identifiants
pubmed: 31436334
doi: 10.15252/embj.2018100811
pmc: PMC6745503
doi:
Substances chimiques
MALAT1 long non-coding RNA, human
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e100811Subventions
Organisme : Medical Research Council
ID : MR/M015688/1
Pays : United Kingdom
Organisme : University of Melbourne De Brettiville Trust
Pays : International
Organisme : The Ophthalmic Research Institute of Australia (ORIA)
Pays : International
Organisme : Kel and Rosie Day Foundation
Pays : International
Organisme : GOSHCC
Pays : International
Informations de copyright
© 2019 The Authors.
Références
Front Cell Neurosci. 2015 Dec 22;9:484
pubmed: 26733810
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Cell Physiol Biochem. 2017;43(5):2117-2132
pubmed: 29065394
Nat Methods. 2017 Sep;14(9):865-868
pubmed: 28759029
Hum Mol Genet. 2010 Jun 15;19(12):2468-86
pubmed: 20360305
Hum Mol Genet. 2010 Nov 1;19(21):4229-38
pubmed: 20709808
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12069-74
pubmed: 17620597
Stem Cells. 2007 Aug;25(8):2033-43
pubmed: 17525239
Genome Biol. 2016 Feb 17;17:29
pubmed: 26887813
Genome Biol. 2016 Apr 27;17:75
pubmed: 27122128
Cell. 2001 Nov 30;107(5):579-89
pubmed: 11733058
Nature. 1999 Feb 11;397(6719):520-2
pubmed: 10028967
Hum Mol Genet. 2004 Jul 15;13(14):1487-503
pubmed: 15163632
Nature. 2019 Feb;566(7744):388-392
pubmed: 30760929
Stem Cells. 2018 Mar;36(3):313-324
pubmed: 29230913
Exp Eye Res. 2014 Dec;129:93-106
pubmed: 25446321
Hum Mol Genet. 2016 Oct 15;25(20):4376-4388
pubmed: 28172828
Sci Rep. 2015 Nov 13;5:16595
pubmed: 26563826
Mol Vis. 2009;15:45-59
pubmed: 19145251
Sci Rep. 2016 Aug 10;6:30552
pubmed: 27506453
Trends Genet. 2016 Oct;32(10):638-659
pubmed: 27615122
Mol Vis. 2011;17:2738-50
pubmed: 22065927
BMC Genomics. 2013 Jul 18;14:486
pubmed: 23865674
J Neurosci. 2008 Jan 9;28(2):548-61
pubmed: 18184797
Prog Retin Eye Res. 2008 Mar;27(2):213-35
pubmed: 18328765
Nat Genet. 2001 Jan;27(1):94-8
pubmed: 11138006
J Med Genet. 2017 Jul;54(7):450-459
pubmed: 28003323
Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):776-787
pubmed: 29392326
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2023-8
pubmed: 19179291
PLoS One. 2016 Mar 28;11(3):e0152687
pubmed: 27019196
J Hepatol. 2015 Mar;62(3):581-9
pubmed: 25457200
J Comp Neurol. 2015 Mar 1;523(4):649-68
pubmed: 25349106
Exp Eye Res. 2019 Jul;184:234-242
pubmed: 31075224
Brain. 2014 Feb;137(Pt 2):433-48
pubmed: 24355709
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Cell. 2019 Feb 21;176(5):1222-1237.e22
pubmed: 30712875
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5388-96
pubmed: 18055785
Dev Cell. 2017 Dec 18;43(6):763-779.e4
pubmed: 29233477
Invest Ophthalmol Vis Sci. 2002 Mar;43(3):864-9
pubmed: 11867609
Cell. 2016 Aug 25;166(5):1308-1323.e30
pubmed: 27565351
Prog Retin Eye Res. 2016 Mar;51:1-40
pubmed: 26113209
Pharmacol Ther. 2017 Sep;177:32-43
pubmed: 28223228
Nucleic Acids Res. 2016 Jul 8;44(12):5773-84
pubmed: 27235414
Eur J Neurosci. 2018 Jun;47(12):1429-1443
pubmed: 29790615
Genome Res. 2015 Dec;25(12):1860-72
pubmed: 26430063
Dev Biol. 2015 Jun 1;402(1):48-60
pubmed: 25794677
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Science. 2018 Oct 12;362(6411):
pubmed: 30309916
Stem Cells. 2018 May;36(5):709-722
pubmed: 29327488
J Neurosci. 1998 Nov 1;18(21):8936-46
pubmed: 9786999
Stem Cell Reports. 2017 Dec 12;9(6):1898-1915
pubmed: 29153988
Eur J Neurosci. 2002 Jan;15(1):63-78
pubmed: 11860507
Hum Mol Genet. 2016 Mar 1;25(5):989-1000
pubmed: 26740550
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601