Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells.
ID proteins
adult neurogenesis
adult stem cell
hippocampus
mouse
neuroscience
quiescence
regenerative medicine
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
25 09 2019
25 09 2019
Historique:
received:
17
05
2019
accepted:
24
09
2019
pubmed:
26
9
2019
medline:
31
3
2020
entrez:
26
9
2019
Statut:
epublish
Résumé
Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.
Identifiants
pubmed: 31552825
doi: 10.7554/eLife.48561
pii: 48561
pmc: PMC6805120
doi:
pii:
Substances chimiques
Ascl1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
Idb4 protein, mouse
0
Inhibitor of Differentiation Proteins
0
Transcription Factor 3
0
Banques de données
GEO
['GSE116997']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome
ID : 106187/Z/14/Z
Pays : International
Organisme : Francis Crick Institute
ID : FC0010089
Pays : International
Organisme : Ligue Contre le Cancer
ID : PJA 20131200481
Pays : International
Organisme : Ligue Contre le Cancer
ID : PJA 20151203259
Pays : International
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : H2020-MSCA-IF-2014
Pays : International
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : Project 799214
Pays : International
Organisme : Medical Research Council
ID : MR/M023907/1
Pays : United Kingdom
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 799214
Pays : International
Organisme : Medical Research Council
ID : U117570528
Pays : United Kingdom
Informations de copyright
© 2019, Blomfield et al.
Déclaration de conflit d'intérêts
IB, BR, MM, EM, SV, Dv, EH, NU No competing interests declared, FG Reviewing editor, eLife
Références
Development. 2017 Oct 1;144(19):3465-3474
pubmed: 28974640
Nat Neurosci. 1999 Apr;2(4):339-45
pubmed: 10204540
Curr Opin Neurobiol. 2013 Dec;23(6):935-42
pubmed: 24090877
J Neurosci. 2013 Oct 30;33(44):17490-505
pubmed: 24174682
Cell Stem Cell. 2015 Sep 3;17(3):360-72
pubmed: 26299571
Cold Spring Harb Perspect Biol. 2015 Dec 04;8(3):a018887
pubmed: 26637286
Curr Top Dev Biol. 2014;110:189-216
pubmed: 25248477
Development. 2014 Aug;141(16):3159-64
pubmed: 25038044
Cell Stem Cell. 2010 Jul 2;7(1):78-89
pubmed: 20621052
Nature. 2012 Sep 6;489(7414):150-4
pubmed: 22842902
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Cell Stem Cell. 2015 Oct 1;17(4):385-95
pubmed: 26431181
Nature. 2017 Mar 9;543(7644):205-210
pubmed: 28241143
BMC Bioinformatics. 2011 Dec 17;12:480
pubmed: 22177264
Neuron. 2014 Apr 2;82(1):9-23
pubmed: 24698265
Development. 2015 May 1;142(9):1572-81
pubmed: 25922523
EMBO J. 2004 Sep 1;23(17):3527-37
pubmed: 15318167
Nat Neurosci. 2007 Jun;10(6):720-6
pubmed: 17468753
Genes Dev. 2019 May 1;33(9-10):511-523
pubmed: 30862661
Elife. 2019 Sep 25;8:
pubmed: 31552825
Cell Stem Cell. 2011 May 6;8(5):566-79
pubmed: 21549330
Nat Biotechnol. 2013 Jan;31(1):46-53
pubmed: 23222703
EMBO Rep. 2018 Mar;19(3):
pubmed: 29335248
Nat Neurosci. 2010 Jan;13(1):133-40
pubmed: 20023653
Nat Biotechnol. 2010 May;28(5):511-5
pubmed: 20436464
Cell Stem Cell. 2017 Nov 2;21(5):604-617.e5
pubmed: 29100013
Science. 2018 Mar 16;359(6381):1277-1283
pubmed: 29590078
Biochimie. 2015 May;112:139-50
pubmed: 25778840
Stem Cells. 2012 Apr;30(4):741-52
pubmed: 22232070
Dev Biol. 2005 Apr 15;280(2):386-95
pubmed: 15882580
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Glia. 2006 Jul;54(1):21-34
pubmed: 16652340
Biochim Biophys Acta. 2015 Jan;1855(1):92-103
pubmed: 25512197
Cell Rep. 2019 Aug 6;28(6):1485-1498.e6
pubmed: 31390563
Cell Stem Cell. 2018 Aug 02;23(2):252-265.e8
pubmed: 30082068
Cold Spring Harb Perspect Biol. 2016 May 02;8(5):
pubmed: 27048191
Nat Cell Biol. 2010 Jan;12(1):31-40; sup pp 1-9
pubmed: 20010817
Dev Cell. 2007 Aug;13(2):283-97
pubmed: 17681138
Neuron. 2018 Aug 8;99(3):493-510.e4
pubmed: 30057205
Nature. 2016 Jan 7;529(7584):37-42
pubmed: 26738589
J Neurosci. 2010 Mar 3;30(9):3489-98
pubmed: 20203209
Science. 2016 Jul 15;353(6296):292-5
pubmed: 27418510
Oncogene. 2015 Jan 2;34(1):53-62
pubmed: 24413082
J Neurosci. 2013 Feb 13;33(7):3010-24
pubmed: 23407958
Nat Neurosci. 2018 Feb;21(2):290-299
pubmed: 29335606
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Cell Rep. 2018 Jan 23;22(4):992-1002
pubmed: 29386140
Nat Cell Biol. 2012 Apr 22;14(5):477-87
pubmed: 22522171
Development. 2004 Sep;131(17):4131-42
pubmed: 15280210
Development. 2004 Nov;131(21):5441-8
pubmed: 15469968
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Cell Stem Cell. 2009 Sep 4;5(3):279-89
pubmed: 19733540
BMC Dev Biol. 2001;1:4
pubmed: 11299042
Cell Rep. 2017 Dec 12;21(11):3271-3284
pubmed: 29241552
Science. 2013 Dec 6;342(6163):1203-8
pubmed: 24179156
Science. 2018 Feb 9;359(6376):658-662
pubmed: 29439238
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E8996-E9005
pubmed: 29073096
Cell Stem Cell. 2015 Sep 3;17(3):329-40
pubmed: 26235341
Genome Biol. 2013 Apr 25;14(4):R36
pubmed: 23618408
Genes Dev. 2011 May 1;25(9):930-45
pubmed: 21536733
J Cell Sci. 2011 Jun 1;124(Pt 11):1867-77
pubmed: 21558414
Nature. 2005 Oct 27;437(7063):1370-5
pubmed: 16251967
Cell. 1990 Apr 6;61(1):49-59
pubmed: 2156629
Immunity. 2018 Feb 20;48(2):271-285.e5
pubmed: 29466757
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Genes Dev. 2013 Aug 15;27(16):1769-86
pubmed: 23964093
J Neurosci. 2008 Sep 10;28(37):9194-204
pubmed: 18784300
Cell Stem Cell. 2009 Nov 6;5(5):515-26
pubmed: 19896442
Neuron. 2014 Sep 3;83(5):1085-97
pubmed: 25189209