A cellular and spatial map of the choroid plexus across brain ventricles and ages.
Age Factors
Aging
/ physiology
Animals
Blood-Brain Barrier
/ metabolism
Brain
/ metabolism
Brain Diseases
/ genetics
Cell Differentiation
/ genetics
Cell Lineage
/ genetics
Choroid Plexus
/ embryology
Epithelial Cells
/ metabolism
Female
Male
Mice
/ embryology
Mice, Inbred C57BL
Signal Transduction
Single-Cell Analysis
aging
brain barrier
cerebrospinal fluid
choroid plexus
development
single-cell RNA sequencing
single-nucleus RNA sequencing
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
27 05 2021
27 05 2021
Historique:
received:
15
04
2019
revised:
15
12
2020
accepted:
02
04
2021
pubmed:
2
5
2021
medline:
22
12
2021
entrez:
1
5
2021
Statut:
ppublish
Résumé
The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1β (IL-1β) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.
Identifiants
pubmed: 33932339
pii: S0092-8674(21)00438-4
doi: 10.1016/j.cell.2021.04.003
pmc: PMC8214809
mid: NIHMS1690857
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3056-3074.e21Subventions
Organisme : NINDS NIH HHS
ID : R01 NS088566
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL110852
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov until July 31, 2020. A.R. has been an employee of Genentech since August 1, 2020. O.R.-R. is an employee of Genentech and co-inventor on patent applications filed by the Broad related to single cell genomics. R.H.H. has been an employee of Immunai since August 16, 2020. A.R., R.H.H., N.H., M.K.L., N.D., and A.J. are co-inventors on a provisional patent application filed by the Broad Institute relating to this manuscript.
Références
Cell Stem Cell. 2016 Nov 3;19(5):643-652
pubmed: 27452173
Nature. 1999 Feb 18;397(6720):617-21
pubmed: 10050855
Nat Biotechnol. 2018 Dec 03;:
pubmed: 30531897
Nat Commun. 2016 Apr 19;7:11022
pubmed: 27090946
Nat Commun. 2021 Jan 19;12(1):447
pubmed: 33469018
Science. 2014 Oct 3;346(6205):89-93
pubmed: 25147279
Bioinformatics. 2016 Apr 15;32(8):1241-3
pubmed: 26668002
Nature. 2018 Feb 22;554(7693):475-480
pubmed: 29443965
Neuron. 2019 Jan 16;101(2):207-223.e10
pubmed: 30606613
Immunity. 2018 Aug 21;49(2):326-341.e7
pubmed: 30054204
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Nat Commun. 2019 Jul 2;10(1):2907
pubmed: 31266958
Nat Genet. 2003 Sep;35(1):70-5
pubmed: 12923530
Nature. 2007 Nov 1;450(7166):56-62
pubmed: 17972876
Science. 2020 Nov 13;370(6518):856-860
pubmed: 33082293
Nature. 2018 Aug;560(7719):494-498
pubmed: 30089906
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D552-6
pubmed: 14681479
PLoS Genet. 2017 Mar 23;13(3):e1006599
pubmed: 28333934
Trends Genet. 2017 Oct;33(10):715-727
pubmed: 28851604
Nature. 2007 Jan 11;445(7124):168-76
pubmed: 17151600
BMC Bioinformatics. 2009 Feb 03;10:48
pubmed: 19192299
Cell. 2018 Aug 9;174(4):1015-1030.e16
pubmed: 30096299
Immunity. 2019 Jan 15;50(1):253-271.e6
pubmed: 30471926
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11388-E11396
pubmed: 30413620
Nature. 2014 May 22;509(7501):507-11
pubmed: 24828040
Cell. 2010 Oct 1;143(1):134-44
pubmed: 20887898
Nat Rev Mol Cell Biol. 2016 Apr;17(4):240-56
pubmed: 26790531
Dev Biol. 2013 Jul 15;379(2):229-34
pubmed: 23648512
Cell Rep. 2019 Jan 8;26(2):394-406.e5
pubmed: 30625322
Development. 2000 Sep;127(18):4061-71
pubmed: 10952903
PLoS Comput Biol. 2007 Mar 23;3(3):e39
pubmed: 17381235
Acta Neuropathol. 2018 Mar;135(3):337-361
pubmed: 29368213
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7821-6
pubmed: 12060727
Nat Immunol. 2009 May;10(5):514-23
pubmed: 19305396
Nat Med. 2017 Aug;23(8):997-1003
pubmed: 28692063
Nat Commun. 2018 Mar 14;9(1):1062
pubmed: 29540683
Cell Rep. 2017 Jan 17;18(3):777-790
pubmed: 28099854
Histochem Cell Biol. 2012 Nov;138(5):709-24
pubmed: 22782339
Nature. 2020 Jul;583(7815):296-302
pubmed: 32612232
Am J Anat. 1966 Jan;118(1):283-316
pubmed: 5915034
J Comp Neurol. 1960 Oct;115:171-86
pubmed: 13716507
Curr Biol. 2014 Oct 6;24(19):R973-82
pubmed: 25291643
Cell. 2019 Feb 7;176(4):928-943.e22
pubmed: 30712874
Brain Res Dev Brain Res. 1990 Oct 1;56(1):47-53
pubmed: 2279331
Development. 2007 Oct;134(19):3449-60
pubmed: 17728348
Cell. 2014 Mar 13;156(6):1223-1234
pubmed: 24630724
Cell Tissue Res. 1989 Mar;255(3):487-94
pubmed: 2706656
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1194-E1203
pubmed: 29358392
PLoS One. 2015 Jun 11;10(6):e0129912
pubmed: 26067061
Dev Cell. 2020 Feb 10;52(3):261-275
pubmed: 32049038
Science. 2019 Jan 25;363(6425):
pubmed: 30679343
Cerebrospinal Fluid Res. 2010 Oct 05;7:16
pubmed: 20920364
Neuron. 2011 Mar 10;69(5):893-905
pubmed: 21382550
JCI Insight. 2019 Dec 5;4(23):
pubmed: 31647782
Dev Cell. 2020 Jul 6;54(1):43-59.e4
pubmed: 32634398
Nat Methods. 2017 Oct;14(10):955-958
pubmed: 28846088
Development. 2009 Aug;136(15):2535-43
pubmed: 19570847
Annu Rev Neurosci. 2009;32:149-84
pubmed: 19555289
Cancer Cell. 2015 May 11;27(5):712-27
pubmed: 25965574
Dev Neurobiol. 2016 Jan;76(1):75-92
pubmed: 25980532
Nat Methods. 2016 Oct;13(10):845-8
pubmed: 27571553
Science. 2020 Jul 10;369(6500):
pubmed: 32527923
Cell Syst. 2019 Apr 24;8(4):329-337.e4
pubmed: 30954475
Physiol Rev. 2013 Oct;93(4):1847-92
pubmed: 24137023
EMBO J. 2014 Jan 7;33(1):7-22
pubmed: 24357543
J Neurosci. 2015 Mar 25;35(12):4903-16
pubmed: 25810521
Immunity. 2013 Mar 21;38(3):555-69
pubmed: 23477737
Mol Cell Neurosci. 2012 Feb;49(2):217-29
pubmed: 22173107
Nat Commun. 2019 Apr 2;10(1):1498
pubmed: 30940800
Science. 2016 Jul 29;353(6298):453
pubmed: 27482552
J Physiol. 2018 Dec;596(23):5723-5756
pubmed: 29774535
Nat Methods. 2017 Sep 29;14(10):935-936
pubmed: 28960196
Brain Behav Immun. 2020 Jul;87:18-22
pubmed: 32240762
Curr Opin Neurobiol. 2001 Feb;11(1):82-8
pubmed: 11179876
Cell Stem Cell. 2020 Dec 3;27(6):951-961.e5
pubmed: 33113348
Dev Biol. 2014 Jun 15;390(2):181-90
pubmed: 24680895
Am J Pathol. 2018 Jun;188(6):1334-1344
pubmed: 29545198
Development. 2008 Mar;135(6):1049-58
pubmed: 18256198
Nat Rev Neurosci. 2015 Aug;16(8):445-57
pubmed: 26174708
Genetics. 2000 Jun;155(2):945-59
pubmed: 10835412
Nature. 2021 Apr;592(7852):128-132
pubmed: 33536623
Lancet Neurol. 2020 Sep;19(9):767-783
pubmed: 32622375
Dev Cell. 2020 Dec 7;55(5):617-628.e6
pubmed: 33038331
Nat Neurosci. 2019 Jun;22(6):1021-1035
pubmed: 31061494
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Science. 1978 Jul 14;201(4351):176-8
pubmed: 663649
J Mol Diagn. 2012 Jan;14(1):22-9
pubmed: 22166544
Nature. 2009 Jan 15;457(7227):318-21
pubmed: 19037245
Nature. 1997 Nov 6;390(6655):45-51
pubmed: 9363890
Cell. 2016 Sep 8;166(6):1500-1511.e9
pubmed: 27610572
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
Cell. 2018 May 3;173(4):1045-1057.e9
pubmed: 29727663
Nature. 2018 Aug;560(7718):319-324
pubmed: 30069044
Neuron. 2020 Nov 25;108(4):623-639.e10
pubmed: 32961128