TY - JOUR
T1 - Single-cell proteomics reveals changes in expression during hair-cell development
AU - Zhu, Ying
AU - Scheibinger, Mirko
AU - Ellwanger, Daniel Christian
AU - Krey, Jocelyn F.
AU - Choi, Dongseok
AU - Kelly, Ryan T.
AU - Heller, Stefan
AU - Barr-Gillespie, Peter G.
N1 - Funding Information:
We thank Pamela Canaday and Matthew Lewis for their assistance with flow cytometry. We received support from the following OHSU core facilities: FACS from the OHSU Flow Cytometry Shared Resource (supported in part by the OHSU Knight Cancer Institute and the NCI Cancer Center Support Grant P30 CA069533) and confocal microscopy from the OHSU Advanced Light Microscopy Core (P30 NS061800 provided support for imaging). We also received support from the following Stanford core facilities: the Stanford Shared FACS Facility, the Stanford Functional Genomics Facility, and the Otolaryngology Imaging Core. Some of the computing for this project was performed on the Sherlock cluster; we thank the Stanford Research Computing Center for providing computational resources and support. YZ was supported by Earth and Biological Sciences Directorate Mission Seed under the Laboratory Directed Research and Development Program at PNNL, and the Precision Medicine Innovation Co-Laboratory (PMedIC), a joint research collaboration of OHSU and PNNL. A portion of the research at PNNL was performed using EMSL (grid.436923.9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. SH was supported by R01 DC015201, by the Hearing Health Foundation’s Hearing Restoration Project, and through the Stanford Initiative to Cure Hearing Loss. RTK was supported by R33 CA225248. PGBG was supported by NIH grant R01 DC011034.
Funding Information:
OHSU Knight Cancer Institute and the NCI Cancer Center Support Grant P30 CA069533 and confocal microscopy from the OHSUAdvanced Light Microscopy Core (P30 NS061800 provided support for imaging). A portion of the research at PNNL was performed using EMSL (grid. 436923.9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. SH was supported by R01 DC015201, by the Hearing Health Foundation?s Hearing Restoration Project and through the Stanford Initiative to Cure Hearing Loss. RTK was supported by R33 CA225248. PGBG was supported by NIH grant R01 DC011034.
Publisher Copyright:
© 2019, eLife Sciences Publications Ltd. All rights reserved.
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.50777
DO - 10.7554/eLife.50777
M3 - Article
C2 - 31682227
AN - SCOPUS:85074962082
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e50777
ER -