Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration.
Animals
Cell Differentiation
Cell Lineage
/ genetics
Cell Survival
Cochlea
/ cytology
Epithelial Cells
/ cytology
Gene Expression Regulation
Genetic Association Studies
Integrases
/ metabolism
Mice
Mitosis
Multigene Family
Protein Biosynthesis
Receptors, G-Protein-Coupled
/ metabolism
Regeneration
/ genetics
Stem Cells
/ cytology
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
31
03
2021
accepted:
18
10
2021
revised:
22
11
2021
pubmed:
11
11
2021
medline:
22
12
2021
entrez:
10
11
2021
Statut:
epublish
Résumé
Cochlear supporting cells (SCs) are glia-like cells critical for hearing function. In the neonatal cochlea, the greater epithelial ridge (GER) is a mitotically quiescent and transient organ, which has been shown to nonmitotically regenerate SCs. Here, we ablated Lgr5+ SCs using Lgr5-DTR mice and found mitotic regeneration of SCs by GER cells in vivo. With lineage tracing, we show that the GER houses progenitor cells that robustly divide and migrate into the organ of Corti to replenish ablated SCs. Regenerated SCs display coordinated calcium transients, markers of the SC subtype inner phalangeal cells, and survive in the mature cochlea. Via RiboTag, RNA-sequencing, and gene clustering algorithms, we reveal 11 distinct gene clusters comprising markers of the quiescent and damaged GER, and damage-responsive genes driving cell migration and mitotic regeneration. Together, our study characterizes GER cells as mitotic progenitors with regenerative potential and unveils their quiescent and damaged translatomes.
Identifiants
pubmed: 34758021
doi: 10.1371/journal.pbio.3001445
pii: PBIOLOGY-D-21-00890
pmc: PMC8608324
doi:
Substances chimiques
Lgr5 protein, mouse
0
Receptors, G-Protein-Coupled
0
Cre recombinase
EC 2.7.7.-
Integrases
EC 2.7.7.-
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
e3001445Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC013817
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001085
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC019370
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003142
Pays : United States
Organisme : NIDCD NIH HHS
ID : K08 DC011043
Pays : United States
Organisme : NIDCD NIH HHS
ID : U01 DC013817
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC013910
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC001910
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Cell Rep. 2017 Feb 21;18(8):1917-1929
pubmed: 28228258
Sci Rep. 2011;1:26
pubmed: 22355545
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9815-9
pubmed: 7568224
Nat Cell Biol. 2017 Jun;19(6):666-676
pubmed: 28553937
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
J Assoc Res Otolaryngol. 2010 Sep;11(3):407-18
pubmed: 20386946
Dev Dyn. 2013 Oct;242(10):1210-21
pubmed: 23813480
Reprod Fertil Dev. 2014;26(4):587-98
pubmed: 23719176
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Development. 2019 Feb 15;146(4):
pubmed: 30770379
J Neurosci. 2012 Feb 29;32(9):3131-41
pubmed: 22378886
J Neurosci. 2017 Jan 11;37(2):258-268
pubmed: 28077706
Cell. 2015 Dec 3;163(6):1348-59
pubmed: 26627734
Compr Physiol. 2017 Sep 12;7(4):1197-1227
pubmed: 28915323
Proc Natl Acad Sci U S A. 2012 May 22;109(21):8167-72
pubmed: 22562792
J Mol Neurosci. 2015 Apr;55(4):836-44
pubmed: 25407819
Nat Neurosci. 2010 Jan;13(1):133-40
pubmed: 20023653
Nature. 2007 Nov 1;450(7166):50-5
pubmed: 17972875
J Assoc Res Otolaryngol. 2011 Aug;12(4):455-69
pubmed: 21472479
J Neurosci. 2013 Jan 23;33(4):1564-76
pubmed: 23345230
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Cell Rep. 2021 Jan 19;34(3):108646
pubmed: 33472062
Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21054-21060
pubmed: 31570588
Nat Commun. 2020 May 13;11(1):2389
pubmed: 32404924
Dev Biol. 2016 Jun 1;414(1):72-84
pubmed: 27090805
Genesis. 2003 Jan;35(1):63-72
pubmed: 12481300
BMC Genomics. 2018 Sep 21;19(1):696
pubmed: 30241496
J Anat. 2016 Feb;228(2):233-54
pubmed: 26052920
Genome Biol. 2014;15(12):550
pubmed: 25516281
Laryngoscope. 2021 Sep;131 Suppl 5:S1-S16
pubmed: 32579737
Purinergic Signal. 2010 Jun;6(2):155-66
pubmed: 20806009
Cell. 2012 Dec 7;151(6):1332-44
pubmed: 23217714
Neuron. 2011 Aug 11;71(3):389-405
pubmed: 21835338
Development. 2015 May 1;142(9):1561-71
pubmed: 25922522
Mol Cell Endocrinol. 2015 May 15;407:1-8
pubmed: 25737207
Tohoku J Exp Med. 2003 Jul;200(3):137-44
pubmed: 14521256
J Clin Invest. 2018 Apr 2;128(4):1641-1656
pubmed: 29553487
Development. 2014 Feb;141(4):816-29
pubmed: 24496619
Elife. 2018 Mar 29;7:
pubmed: 29595471
Development. 1999 Apr;126(8):1581-90
pubmed: 10079221
Stem Cell Reports. 2014 Feb 20;2(3):311-22
pubmed: 24672754
Genesis. 2004 Apr;38(4):195-9
pubmed: 15083520
Biomed Res Int. 2014;2014:367939
pubmed: 25210710
Nature. 2005 Apr 14;434(7035):889-94
pubmed: 15829963
Nature. 2018 Nov;563(7733):696-700
pubmed: 30464345
Annu Rev Cell Dev Biol. 2019 Oct 6;35:567-589
pubmed: 31553635
BMC Genet. 2014 Jan 03;15:1
pubmed: 24387126
Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16919-24
pubmed: 25385613
Int J Biochem Cell Biol. 2015 Jul;64:147-54
pubmed: 25882493
Elife. 2018 Feb 08;7:
pubmed: 29419377
Dev Biol. 2013 Apr 1;376(1):86-98
pubmed: 23318633
Neuron. 2008 Jan 24;57(2):263-75
pubmed: 18215623
J Neurosci. 2004 Oct 6;24(40):8651-61
pubmed: 15470130
PLoS Biol. 2019 Nov 12;17(11):e3000481
pubmed: 31714939
J Mol Biol. 2019 Jun 14;431(13):2398-2406
pubmed: 31100387
Elife. 2019 Jan 25;8:
pubmed: 30681411
Science. 1996 Jul 26;273(5274):507-10
pubmed: 8662541
J Assoc Res Otolaryngol. 2008 Mar;9(1):65-89
pubmed: 18157569
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Front Cell Neurosci. 2018 Nov 14;12:407
pubmed: 30524238
J Neurosci. 2006 Jul 19;26(29):7659-64
pubmed: 16855093
J Clin Invest. 2015 Feb;125(2):583-92
pubmed: 25555219
Cell Stem Cell. 2011 Oct 4;9(4):317-29
pubmed: 21982232
Genesis. 2005 Nov;43(3):129-35
pubmed: 16267821
Development. 1998 Sep;125(18):3709-18
pubmed: 9716536
Mol Biol Cell. 2007 Apr;18(4):1507-18
pubmed: 17314409
NPJ Regen Med. 2018 Feb 23;3:6
pubmed: 29507774
Cell Signal. 2012 Apr;24(4):943-50
pubmed: 22230687
Nature. 2011 Sep 18;478(7368):255-9
pubmed: 21927002
J Assoc Res Otolaryngol. 2009 Mar;10(1):37-49
pubmed: 19082858
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13939-44
pubmed: 19666516
Gene. 2018 Jul 20;664:152-167
pubmed: 29679756
Elife. 2016 Dec 14;5:
pubmed: 27966429
PLoS One. 2009 Nov 11;4(11):e7786
pubmed: 19936227
J Neurosci. 2015 May 20;35(20):7878-91
pubmed: 25995473