Single-cell proteomics reveals downregulation of TMSB4X to drive actin release for stereocilia assembly

Autor: Mirko Scheibinger, Ying Zhu, Daniel C. Ellwanger, Stefan Heller, Jocelyn F. Krey, Ryan T. Kelly, Dongseok Choi, Peter G. Barr-Gillespie
Jazyk: angličtina
Rok vydání: 2019
Předmět:
DOI: 10.1101/727412
Popis: Hearing and balance rely on small sensory hair cells that reside in the inner ear. To explore dynamic changes in the abundant proteins present in differentiating hair cells, we used nanoliter-scale shotgun mass spectrometry of single cells, each ∼1 picoliter, from utricles of embryonic day 15 chickens. We identified unique constellations of proteins or protein groups from presumptive hair cells and from progenitor cells. The single-cell proteomes enabled thede novoreconstruction of a developmental trajectory. Inference of protein expression dynamics revealed that the actin monomer binding protein thymosin β4 (TMSB4X) was present in progenitors but dropped precipitously during hair-cell differentiation. Complementary single-cell transcriptome profiling showed downregulation ofTMSB4XmRNA during maturation of hair cells. We propose that most actin is sequestered by TMSB4X in progenitor cells, but upon differentiation to hair cells, actin is released to build the sensory hair bundle.
Databáze: OpenAIRE