Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes.
Animals
Antibiotics, Antineoplastic
/ metabolism
Basement Membrane
/ cytology
Blood-Brain Barrier
/ cytology
Cell Communication
Cell Surface Extensions
/ metabolism
Cytoplasmic Vesicles
/ metabolism
Doxorubicin
/ metabolism
Endothelial Cells
/ cytology
Female
Growth Substances
/ metabolism
Hippocampus
/ cytology
Male
Mice
Neural Stem Cells
/ cytology
Neurogenesis
adult neurogenesis
blood-brain-barrier
chemobrain
dentate gyrus
mouse
neuroscience
neurovascular unit
regenerative medicine
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
23
09
2019
accepted:
03
06
2020
pubmed:
5
6
2020
medline:
4
3
2021
entrez:
5
6
2020
Statut:
epublish
Résumé
Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG(have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30 nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.
Identifiants
pubmed: 32496193
doi: 10.7554/eLife.52134
pii: 52134
pmc: PMC7297534
doi:
pii:
Substances chimiques
Antibiotics, Antineoplastic
0
Growth Substances
0
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : H2020 European Research Council
ID : 322692
Pays : International
Organisme : Israel Science Foundation
ID : 1882/16
Pays : International
Organisme : Israel Science Foundation
ID : 2402/16
Pays : International
Informations de copyright
© 2020, Licht et al.
Déclaration de conflit d'intérêts
TL, ES, BB, MG, SK, TK, AB, EK No competing interests declared
Références
Cell Stem Cell. 2011 May 6;8(5):566-79
pubmed: 21549330
Clin Cancer Res. 2012 Apr 1;18(7):1954-65
pubmed: 22338017
Behav Brain Res. 2016 Dec 15;315:10-22
pubmed: 27478140
Nature. 2014 May 22;509(7501):507-11
pubmed: 24828040
J Neurosci. 2017 Oct 18;37(42):10052-10062
pubmed: 28912161
Development. 2010 Jan;137(2):261-71
pubmed: 20040492
Nat Med. 2015 Aug;21(8):932-7
pubmed: 26147761
Stem Cell Reports. 2019 Apr 9;12(4):667-679
pubmed: 30905740
Bioinformatics. 2014 Aug 15;30(16):2389-90
pubmed: 24771516
Int J Cancer. 2007 Aug 15;121(4):901-7
pubmed: 17437269
J Comp Neurol. 2004 Feb 9;469(3):311-24
pubmed: 14730584
Nature. 2002 Feb 28;415(6875):1030-4
pubmed: 11875571
Nature. 2011 Aug 31;477(7362):90-4
pubmed: 21886162
Cell. 2004 Aug 20;118(4):505-16
pubmed: 15315762
J Comp Neurol. 2000 Oct 2;425(4):479-94
pubmed: 10975875
Mol Cell Neurosci. 2003 Jul;23(3):373-82
pubmed: 12837622
Mech Dev. 2015 Nov;138 Pt 1:56-62
pubmed: 26103548
J Clin Invest. 2015 Mar 2;125(3):1319-28
pubmed: 25689256
Cold Spring Harb Perspect Med. 2018 Apr 2;8(4):
pubmed: 28495803
Eur J Neurosci. 2003 Nov;18(10):2803-12
pubmed: 14656329
Behav Brain Res. 2015 Oct 1;292:184-93
pubmed: 26057360
J Cereb Blood Flow Metab. 2017 Oct;37(10):3300-3317
pubmed: 28753105
Behav Brain Res. 2017 Jan 15;317:332-339
pubmed: 27702635
Cell Metab. 2016 Aug 9;24(2):332-40
pubmed: 27345423
Nat Med. 2014 Jun;20(6):659-63
pubmed: 24793238
Cancer Invest. 2010 Jun;28(5):544-53
pubmed: 20014946
Curr Med Chem. 2014;21(19):2190-207
pubmed: 24372220
Sci Rep. 2018 Nov 23;8(1):17293
pubmed: 30470794
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7828-E7836
pubmed: 27849577
J Neurosci. 2012 Nov 14;32(46):16435-48
pubmed: 23152626
Cell. 2011 Jun 24;145(7):1142-55
pubmed: 21664664
Autoimmun Rev. 2013 Apr;12(6):674-7
pubmed: 23201925
Neuropharmacology. 2018 May 1;133:451-461
pubmed: 29477301
Nature. 2017 Apr 27;544(7651):488-492
pubmed: 28424512
Stem Cells. 2016 Apr;34(4):997-1010
pubmed: 26729510
Science. 2018 Feb 9;359(6376):658-662
pubmed: 29439238
Cell Stem Cell. 2008 Sep 11;3(3):265-78
pubmed: 18786414
Nature. 2016 Jan 21;529(7586):316-25
pubmed: 26791722
Proc Natl Acad Sci U S A. 2016 May 3;113(18):E2536-45
pubmed: 27091993
Science. 2014 May 9;344(6184):630-4
pubmed: 24797482
Biochem Pharmacol. 1995 May 17;49(10):1541-4
pubmed: 7763297
Cancer Chemother Pharmacol. 2019 Jul;84(1):1-14
pubmed: 30955080