November 17 Nov 17
2023
Friday Fri

Meeting Details:

2:00PM-2:30PM - Refreshments
2:30PM-3:30PM - Seminar
Tung Auditorium, Biomedical Innovations Bldg – Room 1021

Host: Dr. Teresa Nicolson

Sensory hair cell regeneration in the zebrafish – how to turn the lateral line into an ear

Tatjana Piotrowski, PhD, Stowers Institute for Medical Research

Hearing loss in mammals is due to the lack of regeneration in the cochlea after the death of mechanosensory hair cells. Regenerating hair cells is a central strategy for restoring hearing, but triggering proliferative regeneration and maturation of hair cells remains elusive. Zebrafish have an array of mechanosensory hair cell-containing neuromasts along the trunk, called the lateral line. Zebrafish hair cells share genetic, functional, and structural similarity with mammalian inner ear hair cells, but zebrafish hair cells readily and rapidly regenerate following death to restore full function.  We have characterized the transcriptional changes during regeneration in the lateral line in a fine time scale using scRNA-seq. We identified three subsequently activated gene modules that serve as a blueprint to trigger regeneration in mammals. The transcription factor prdm1a is upregulated in the third module and expressed in hair cells of the lateral line, but not in hair cells of the zebrafish or mammalian inner ear. Previously, prdm1 has been shown to control a fate switch in various cell types, including B lymphocytes and photoreceptors in the retina. We mutated prdm1a in zebrafish and found a cell type fate switch between lateral line and inner ear hair cells, with many specific inner ear hair cell genes ectopically expressed in lateral line hair cells of the mutants. We performed ATAC-seq and ChIP-seq to characterize enhancers and binding motifs that allowed us to build a gene regulatory network that resembles inner versus outer hair cell fate decisions in the mouse. Prdm1a plays an important role in hair cell evolution but might also have implications for triggering hair cell regeneration in the mouse.

Speaker

Tatjana Piotrowski, PhD
Investigator
Stowers Institute for Medical Research

Location

Stanford University School of Medicine
240 Pasteur Dr. Rm 1021
Palo Alto, CA 94304
USA

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Stanford University School of Medicine

240 Pasteur Dr. Rm 1021
Palo Alto, CA 94304
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