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Single-Cell Proteomics

Averaged measurements could present the common pattern shared among the sample but not the individual information contained in different cells, which is so-called cellular heterogeneity. The decompositions of heterogeneity may uncover much functionally-important information, as stated below.

Single-cell transcriptomics and genomics have made tremendous impact on biology research, including cancer biology [1], developmental biology [2], stem cell biology [3], and neuroscience [4]. However, the nucleic-acid–based approaches are blind to proteins, which are the primary effectors of function in biology. Single-cell proteomics has been a dream of biologists for a long time and the recent mass spectrometry (MS)-based proteomic technique development has made the dream possible, Figure 1.

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Figure 1. A dream of single-cell proteomics. Adapted from reference [5].

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MS-based SCP will drastically advance our understanding of human health and disease, especially with the combination of single-cell transcriptomics and genomics (single-cell multiomics). [6,7] However, it still has some technical challenges, including preparation of the tiny amount of proteins in single cells for MS measurements and ultrasensitive detection and identification of proteins using MS. [5] Recently, our lab developed a novel Nano3 technique for preparation of a small number of human cells (i.e., 10 HeLa cells), enabling the identification of over 1000 proteins and dozens of transcription factors from only 10 HeLa cells. (Figure 2) [8]

Figure 2. The scheme of our Nanoparticle-Aided Nanoreactor for Nanoproteomics (Nano3).

References

[1] Baslan T, et al. Nat Rev Cancer. 2017. PMID: 28835719

[2] Farrell JA, et al. Science. 2018. PMID: 29700225

[3] Etzrodt M, et al. Cell Stem Cell. 2014. PMID: 25517464

[4] Poulin JF, et al. Nat Neurosci. 2016. PMID: 27571192

[5] Marx V. Nat Methods. 2019. PMID: 31406385

[6] Slavov N. Science. 2020. PMID: 32001644

[7] Vistain LF, et al. Trends in Biochemical Sciences. 2021. PMID: 33653632

[8] Yang Z, et al. Anal Chem. 2021. PMID: 34297524

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