PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

In Vivo Interplay between p27(Kip1), GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice.

Abstract Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs) are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs) declines abruptly after postnatal maturation. We find that combining p27(Kip1) deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27(Kip1) deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates auditory HC regeneration and suggest p27(Kip1), GATA3, and POU4F3 as additional therapeutic targets for ATOH1-mediated HC regeneration.
PMID
Related Publications

A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability.

Age-dependent in vivo conversion of mouse cochlear pillar and Deiters' cells to immature hair cells by Atoh1 ectopic expression.

TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1.

Regulation of POU4F3 gene expression in hair cells by 5' DNA in mice.

In vivo generation of immature inner hair cells in neonatal mouse cochleae by ectopic Atoh1 expression.

Authors

Mayor MeshTerms
Keywords

aging

cancer

cochlea

development

differentiation

hearing

proliferation

regeneration

sensory

Journal Title cell reports
Publication Year Start




PMID- 28402854
OWN - NLM
STAT- MEDLINE
DA  - 20170413
DCOM- 20170501
LR  - 20170501
IS  - 2211-1247 (Electronic)
VI  - 19
IP  - 2
DP  - 2017 Apr 11
TI  - In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory 
      Cells to Hair Cells in Adult Mice.
PG  - 307-320
LID - S2211-1247(17)30390-X [pii]
LID - 10.1016/j.celrep.2017.03.044 [doi]
AB  - Hearing loss is widespread and persistent because mature mammalian auditory hair 
      cells (HCs) are nonregenerative. In mice, the ability to regenerate HCs from
      surrounding supporting cells (SCs) declines abruptly after postnatal maturation. 
      We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts
      this age-related decline, leading to conversion of SCs to HCs in mature mouse
      cochleae and after noise damage. p27Kip1 deletion, independent of canonical
      effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is
      lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted
      conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted
      mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates
      auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional
      therapeutic targets for ATOH1-mediated HC regeneration.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Walters, Bradley J
AU  - Walters BJ
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Coak, Emily
AU  - Coak E
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Dearman, Jennifer
AU  - Dearman J
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Bailey, Grace
AU  - Bailey G
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Yamashita, Tetsuji
AU  - Yamashita T
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Kuo, Bryan
AU  - Kuo B
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA.
FAU - Zuo, Jian
AU  - Zuo J
AD  - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 
      Memphis, TN 38105, USA. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Atoh1 protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Cdkn1b protein, mouse)
RN  - 0 (GATA3 Transcription Factor)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Pou4f3 protein, mouse)
RN  - 0 (Transcription Factor Brn-3C)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Basic Helix-Loop-Helix Transcription Factors/*biosynthesis/genetics
MH  - Cell Proliferation/genetics
MH  - Cochlea/growth & development/pathology
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - GATA3 Transcription Factor/*biosynthesis/genetics
MH  - Gene Expression Regulation, Developmental
MH  - Hair Cells, Auditory/metabolism/pathology
MH  - Hearing Loss/*genetics/pathology
MH  - Homeodomain Proteins/*biosynthesis/genetics
MH  - Humans
MH  - Mice
MH  - Regeneration/genetics
MH  - Signal Transduction/genetics
MH  - Transcription Factor Brn-3C/*biosynthesis/genetics
OTO - NOTNLM
OT  - aging
OT  - cancer
OT  - cochlea
OT  - development
OT  - differentiation
OT  - hearing
OT  - proliferation
OT  - regeneration
OT  - sensory
EDAT- 2017/04/14 06:00
MHDA- 2017/05/02 06:00
CRDT- 2017/04/14 06:00
PHST- 2016/09/02 [received]
PHST- 2016/11/28 [revised]
PHST- 2017/03/14 [accepted]
AID - S2211-1247(17)30390-X [pii]
AID - 10.1016/j.celrep.2017.03.044 [doi]
PST - ppublish
SO  - Cell Rep. 2017 Apr 11;19(2):307-320. doi: 10.1016/j.celrep.2017.03.044.

<?xml version="1.0" encoding="UTF-8"?>
<b:Sources SelectedStyle="" xmlns:b="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"  xmlns="http://schemas.openxmlformats.org/officeDocument/2006/bibliography" >
</b:Sources>