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TRIM71 reactivation enhances the mitotic and hair cell-forming potential of cochlear supporting cells

Xiao-Jun Li1, Charles Morgan1, Prathamesh T Nadar-Ponniah1

  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

EMBO Reports
|July 26, 2023
PubMed

Insights

Reactivating TRIM71 in mature cochlear supporting cells restores their ability to regenerate hair cells, offering new hope for treating deafness. This regeneration involves de-differentiation into progenitor-like cells.

Area of Science:

  • Oto-neuroscience
  • Developmental Biology
  • Regenerative Medicine

Background:

  • Cochlear hair cell loss is a primary cause of human deafness.
  • Supporting cells in the cochlea can regenerate hair cells, but this capacity diminishes with maturation.
  • Previous research showed LIN28B reactivation restores hair cell regeneration potential in mature supporting cells.

Purpose of the Study:

  • To identify novel factors that enhance the regenerative potential of mature cochlear supporting cells.
  • To investigate the role of TRIM71, a LIN28B target, in supporting cell plasticity and hair cell regeneration.
  • To elucidate the molecular mechanisms underlying TRIM71-mediated regeneration.

Main Methods:

  • Utilized an organoid-based assay to study cochlear supporting cells.
  • Re-expressed TRIM71 in mature (postnatal day 5) mouse cochlear supporting cells.
  • Performed transcriptomic analysis to identify gene modules regulated by TRIM71 and LIN28B.

Main Results:

  • TRIM71 re-expression significantly increased the mitotic and hair cell-forming potential of mature supporting cells.
  • TRIM71 facilitates the de-differentiation of supporting cells into progenitor-like cells, essential for regeneration.
  • TRIM71's RNA-binding activity is crucial for its regenerative function.
  • Identified gene modules linked to TRIM71 and LIN28B-mediated supporting cell reprogramming.
  • The TRIM71-LIN28B target Hmga2 is vital for supporting cell self-renewal and hair cell formation.

Conclusions:

  • TRIM71 is a potent enhancer of cochlear supporting cell plasticity and hair cell regeneration.
  • TRIM71 promotes regeneration by facilitating supporting cell de-differentiation via its RNA-binding activity.
  • The TRIM71-LIN28B-Hmga2 axis represents a key pathway for restoring auditory sensory cells and offers therapeutic targets for hearing loss.
Keywords:
Lin28bTrim71cochleahair cell regenerationsupporting cell reprogramming

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