TY - JOUR
T1 - TRIM71 reactivation enhances the mitotic and hair cell–forming potential of cochlear supporting cells
AU - Li, Xiao Jun
AU - Morgan, Charles
AU - Nadar-Ponniah, Prathamesh T.
AU - Kolanus, Waldemar
AU - Doetzlhofer, Angelika
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/9/6
Y1 - 2023/9/6
N2 - Cochlear hair cell loss is a leading cause of deafness in humans. Neighboring supporting cells have some capacity to regenerate hair cells. However, their regenerative potential sharply declines as supporting cells undergo maturation (postnatal day 5 in mice). We recently reported that reactivation of the RNA-binding protein LIN28B restores the hair cell–regenerative potential of P5 cochlear supporting cells. Here, we identify the LIN28B target Trim71 as a novel and equally potent enhancer of supporting cell plasticity. TRIM71 is a critical regulator of stem cell behavior and cell reprogramming; however, its role in cell regeneration is poorly understood. Employing an organoid-based assay, we show that TRIM71 re-expression increases the mitotic and hair cell–forming potential of P5 cochlear supporting cells by facilitating their de-differentiation into progenitor-like cells. Our mechanistic work indicates that TRIM71's RNA-binding activity is essential for such ability, and our transcriptomic analysis identifies gene modules that are linked to TRIM71 and LIN28B-mediated supporting cell reprogramming. Furthermore, our study uncovers that the TRIM71-LIN28B target Hmga2 is essential for supporting cell self-renewal and hair cell formation.
AB - Cochlear hair cell loss is a leading cause of deafness in humans. Neighboring supporting cells have some capacity to regenerate hair cells. However, their regenerative potential sharply declines as supporting cells undergo maturation (postnatal day 5 in mice). We recently reported that reactivation of the RNA-binding protein LIN28B restores the hair cell–regenerative potential of P5 cochlear supporting cells. Here, we identify the LIN28B target Trim71 as a novel and equally potent enhancer of supporting cell plasticity. TRIM71 is a critical regulator of stem cell behavior and cell reprogramming; however, its role in cell regeneration is poorly understood. Employing an organoid-based assay, we show that TRIM71 re-expression increases the mitotic and hair cell–forming potential of P5 cochlear supporting cells by facilitating their de-differentiation into progenitor-like cells. Our mechanistic work indicates that TRIM71's RNA-binding activity is essential for such ability, and our transcriptomic analysis identifies gene modules that are linked to TRIM71 and LIN28B-mediated supporting cell reprogramming. Furthermore, our study uncovers that the TRIM71-LIN28B target Hmga2 is essential for supporting cell self-renewal and hair cell formation.
KW - Lin28b
KW - Trim71
KW - cochlea
KW - hair cell regeneration
KW - supporting cell reprogramming
UR - http://www.scopus.com/inward/record.url?scp=85165591754&partnerID=8YFLogxK
U2 - 10.15252/embr.202256562
DO - 10.15252/embr.202256562
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C2 - 37492931
AN - SCOPUS:85165591754
SN - 1469-221X
VL - 24
JO - EMBO Reports
JF - EMBO Reports
IS - 9
M1 - e56562
ER -