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Title: Single-cell proteomics reveals changes in expression during hair-cell development

Abstract

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 the de novo reconstruction of a developmental trajectory using protein expression levels, revealing proteins that greatly increased in expression during differentiation of hair cells (e.g., OCM, CRABP1, GPX2, AK1, GSTO1) and those that decreased during differentiation (e.g., TMSB4X, AGR3). Complementary single-cell transcriptome profiling showed corresponding changes in mRNA during maturation of hair cells. Single-cell proteomics data thus can be mined to reveal features of cellular development that may be missed with transcriptomics.

Authors:
ORCiD logo [1];  [2];  [3];  [4];  [5]; ORCiD logo [6];  [2]; ORCiD logo [4]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab.
  2. Stanford Univ., Stanford, CA (United States). Dept. of Otolaryngology Head and Neck Surgery
  3. Stanford Univ., Stanford, CA (United States). Dept. of Otolaryngology Head and Neck Surgery; Amgen Inc., South San Francisco, CA (United States). Genome Analysis Unit, Amgen Research
  4. Oregon Health & Science Univ., Portland, OR (United States). Oregon Hearing Research Center and Vollum Inst.
  5. Oregon Health & Science Univ., Portland, OR (United States). OHSU-PSU School of Public Health; Kyung Hee Univ., Seoul (Republic of Korea). Graduate School of Dentistry
  6. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab.; Brigham Young Univ., Provo, UT (United States). Dept. of Chemistry and Biochemistry
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1575404
Report Number(s):
PNNL-SA-144744
Journal ID: ISSN 2050-084X
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Zhu, Ying, Scheibinger, Mirko, Ellwanger, Daniel Christian, Krey, Jocelyn F., Choi, Dongseok, Kelly, Ryan T., Heller, Stefan, and Barr-Gillespie, Peter G. Single-cell proteomics reveals changes in expression during hair-cell development. United States: N. p., 2019. Web. doi:10.7554/eLife.50777.
Zhu, Ying, Scheibinger, Mirko, Ellwanger, Daniel Christian, Krey, Jocelyn F., Choi, Dongseok, Kelly, Ryan T., Heller, Stefan, & Barr-Gillespie, Peter G. Single-cell proteomics reveals changes in expression during hair-cell development. United States. doi:10.7554/eLife.50777.
Zhu, Ying, Scheibinger, Mirko, Ellwanger, Daniel Christian, Krey, Jocelyn F., Choi, Dongseok, Kelly, Ryan T., Heller, Stefan, and Barr-Gillespie, Peter G. Mon . "Single-cell proteomics reveals changes in expression during hair-cell development". United States. doi:10.7554/eLife.50777. https://www.osti.gov/servlets/purl/1575404.
@article{osti_1575404,
title = {Single-cell proteomics reveals changes in expression during hair-cell development},
author = {Zhu, Ying and Scheibinger, Mirko and Ellwanger, Daniel Christian and Krey, Jocelyn F. and Choi, Dongseok and Kelly, Ryan T. and Heller, Stefan and Barr-Gillespie, Peter G.},
abstractNote = {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 the de novo reconstruction of a developmental trajectory using protein expression levels, revealing proteins that greatly increased in expression during differentiation of hair cells (e.g., OCM, CRABP1, GPX2, AK1, GSTO1) and those that decreased during differentiation (e.g., TMSB4X, AGR3). Complementary single-cell transcriptome profiling showed corresponding changes in mRNA during maturation of hair cells. Single-cell proteomics data thus can be mined to reveal features of cellular development that may be missed with transcriptomics.},
doi = {10.7554/eLife.50777},
journal = {eLife},
number = ,
volume = 8,
place = {United States},
year = {2019},
month = {11}
}

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