Publications

Here, you will find background information on published research articles from Dr. Aleks along with a full list of publications. 

Single-cell proteomics: methods

Measuring hundreds to thousands of proteins in single cells has long been a challenge; unlike DNA and RNA, proteins cannot be amplified for analysis. I contributed to the pioneering method named SCoPE2, that enabled the quantification of 1000s of proteins in single mammalian cells through the use of mass spectrometry (MS). Through quick learning and dexterity, I was able to prepare many 100s of single cells for MS analysis, enabling the demonstration of a high throughput single- cell proteomics workflow with dramatically increased protein quantification. We were able to confidently quantify over 3000 proteins in over 1400 mammalian cells utilizing novel computational algorithms and found evidence of a gradient of extensive proteome heterogeneity within cell populations that are widely thought to be relatively homogeneous. After working on building the SCoPE2 methodology, I became invested in making SCoPE2 more widely used in laboratories.  In the spirit of making SCoPE2 more accessible, I co-led an effort in writing an in-depth protocol paper detailing SCoPE2, published in Nature Protocols and visually demonstrated in JoVE. I have also contributed to the development of pSCoPE, which enabled the consistent prioritization of desired peptides in single-cell analyses by MS. This work optimized the usage of the instrument’s time spent of analyzing identifiable peptides, which increased proteome coverage and data completeness across runs. 

(previously: bioRxiv preprint: doi: https://doi.org/10.1101/2022.03.16.484655)

(previously bioRxiv preprint: doi: https://doi.org/10.1101/2021.03.12.435034)

Single-cell proteomics: applied

After working on SCoPE2, I sought to apply the single-cell proteomics platform towards biological questions in mammalian development. In a work of which I am co-first author and is still under review, we wanted to understand a fundamental question – when do sister cells within the same embryo begin exhibiting differences that are functionally relevant? Through single-cell protein measurements of sister cells from early-stage embryos, I found a remarkable pattern of proteome asymmetry between sister cells that was consistent among many early- stage embryos, an observation that was unable to be previously observed using single-cell RNA sequencing. This striking asymmetry enabled the consistent clustering of sister cells into two opposing groups, which we termed alpha and beta cells. Furthermore, I found that protein degradation and protein transport are the most likely biological processes driving this breakage in symmetry. These observations were recapitulated in the zygote, strongly suggesting that differences in development arise posttranscriptionally, and in human 2-cell embryos, demonstrating concordance across species. Most importantly, I found that cell classification was linked to developmental potential - more specifically, that beta cells resulted in healthier embryos. Overall, this research has provided evidence for early symmetry breaking in mammalian cells that is functionally relevant, a key observation that changes the traditional view of early developmental trajectories. 

In another work that is published in Molecular Human Reproduction, I prepared and analyzed dozens of single human oocytes to understand the effects of advanced maternal age on oocyte quality. We found a number of proteins and protein complexes that are known to be involved in proteostasis and meiosis were differentially abundant among young and old women and during final stages of meiotic maturation. Such markers can guide other studies into development of new treatment options for age-related fertility challenges.


List of Publications


Pending Papers

Petelski, A.A.*, Iwamoto-Stohl, L.K.*, … Slavov, N., Zernicka-Goetz, M. (In Review). Proteome asymmetry in mouse and human embryos before fate specification. https://www.biorxiv.org/content/10.1101/2024.08.26.609777v1.abstract 


Published Papers

Galatidou, S., Petelski A.A., … Slavov, N., Barragan, M. Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes. Molecular Human Reproduction, 30. doi: https://doi.org/10.1093/molehr/gaae023.

(previously: bioRxiv preprint: https://www.biorxiv.org/content/10.1101/2024.05.23.595547v1)


Gatto, L., … Petelski, A.A., … Slavov, N. (2023). Initial recommendations for performing, benchmarking and reporting single-cell proteomics experiments. Nature Methods, 20, 375 – 386. https://doi.org/10.1038/s41592-023-01785-3

(previously: aRxiv preprint doi: https://doi.org/10.48550/arXiv.2207.10815)


Huffman, R.G., … Petelski, A.A., … Slavov, N. (2023). Prioritized mass spectrometry increases the depth, sensitivity and data completeness of single-cell proteomics. Nature Methods, doi: https://doi.org/10.1038/s41592-023-01830-1 

(previously: bioRxiv preprint: doi: https://doi.org/10.1101/2022.03.16.484655)


Petelski, A.A., Slavov, N., & Specht, H. (2022). Single-cell proteomics preparation for mass spectrometry analysis using freeze-heat lysis and an isobaric carrier. Journal of Visualized Experiments, https://pmc.ncbi.nlm.nih.gov/articles/PMC10027359/ 


Petelski, A.A.*, Emmott, E.*, … Slavov, N. (2021). Multiplexed single-cell proteomics using SCoPE2. Nature Protocols, 16, 5398 – 5421. https://doi.org/10.1038/s41596-021-00616-z 

(previously bioRxiv preprint: doi: 10.1101/2021.03.12.435034)


** Kastan, N., Gnedeva, K., Alisch, T., Petelski A.A., … Hudspeth, A.J. (2021). Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues. Nature Communications, 12, 3100. https://doi.org/10.1038/s41467-021-23395-3 


Specht, H., Emmott, E., Petelski, A.A., … Slavov, N. (2021). Single-cell proteomic and transcriptomic analysis of macrophage heterogeneity using SCoPE2. Genome Biol, 22, 50. https://doi.org/10.1186/s13059-021-02267-5 


Petelski, A.A. & Slavov, N. (2020). Analyzing ribosome remodeling in health and disease. Proteomics, 20, 17-18. https://doi.org/10.1002/pmic.202000039 


Gnedeva K., Jacobo A., Salvi J.D., Petelski A.A., & Hudspeth, AJ. (2017). Elastic force restricts growth of the murine utricle. eLife, doi: https://doi.org/10.7554/eLife.25681 


 

* co-first authors.

** pending patent application for derivative of Lats inhibitor presented in this publication.