Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells

Zhu, Ying; Piehowski, Paul D.; Zhao, Rui; Chen, Jing; Shen, Yufeng; Moore, Ronald J.; Shukla, Anil K.; Petyuk, Vladislav A.; Campbell-Thompson, Martha; Mathews, Clayton E.; Smith, Richard D.; Qian, Wei-Jun; Kelly, Ryan T.

doi:10.1038/s41467-018-03367-w

Title: Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells

Journal Article · Wed Feb 28 00:00:00 EST 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-03367-w· OSTI ID:1432521

Zhu, Ying ^[1];

^[2]; Zhao, Rui ^[1];

^[3]; Shen, Yufeng ^[2]; Moore, Ronald J. ^[2]; Shukla, Anil K. ^[2];

^[2]; Campbell-Thompson, Martha ^[3]; Mathews, Clayton E. ^[3];

^[2];

^[1]

Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division
Univ. of Florida, Gainesville, FL (United States). Dept. of Pathology, Immunology and Laboratory Medicine

Nanoscale or single cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (Nanodroplet Processing in One pot for Trace Samples) platform as a major advance in overall sensitivity. NanoPOTS dramatically enhances the efficiency and recovery of sample processing by downscaling processing volumes to <200 nL to minimize surface losses. When combined with ultrasensitive LC-MS, nanoPOTS allows identification of ~1500 to ~3,000 proteins from ~10 to ~140 cells, respectively. By incorporating the Match Between Runs algorithm of MaxQuant, >3000 proteins were consistently identified from as few as 10 cells. Furthermore, we demonstrate robust quantification of ~2400 proteins from single human pancreatic islet thin sections from type 1 diabetic and control donors, illustrating the application of nanoPOTS for spatially resolved proteome measurements from clinical tissues.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-76RL01830; R21 EB020976; R33 CA225248; P41 GM103493; UC4 DK104167; DP3 DK110844; 1S10OD016350-01

OSTI ID:: 1432521

Alternate ID(s):: OSTI ID: 1513201

Report Number(s):: PNNL-SA-125235; PII: 3367

Journal Information:: Nature Communications, Vol. 9, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 291 works

Citation information provided by
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