Yitong Ma

All Publications

• EasyFlow: An open-source, user-friendly cytometry analyzer with graphic user interface (GUI). PloS one Ma, Y., Eizenberg-Magar, I., Antebi, Y. 2024; 19 (11): e0308873

  Abstract

  Flow cytometry enables quantitative measurements of fluorescence in single cells. The technique was widely used for immunology to identify populations with different surface protein markers. More recently, the usage of flow cytometry has been extended to additional readouts, including intracellular proteins and fluorescent protein transgenes, and is widely utilized to study developmental biology, systems biology, microbiology, and many other fields. A common file format (FCS format, defined by the International Society for Advancement of Cytometry (ISAC)) has been universally adopted, facilitating data exchange between different machines. A diverse spectrum of software packages has been developed for the analysis of flow cytometry data. However, those are either 1) costly proprietary softwares, 2) open source packages with prerequisite installation of R or Python and sometimes require users to have experience in coding, or 3) online tools that are limiting for analysis of large data sets. Here, we present EasyFlow, an open-source flow cytometry analysis graphic user interface (GUI) based on Matlab or Python, that can be installed and run locally across platforms (Windows, MacOS, and Linux) without requiring previous coding knowledge. The Python version (EasyFlowQ) is also developed on a popular plotting framework (Matplotlib) and modern user interface toolkit (Qt), allowing more advanced users to customize and keep contributing to the software, as well as its tutorials. Overall, EasyFlow serves as a simple-to-use tool for inexperienced users with little coding experience to use locally, as well as a platform for advanced users to further customize for their own needs.

  View details for DOI 10.1371/journal.pone.0308873

  View details for PubMedID 39536028

• The realization of CRISPR gene therapy. Nature chemical biology Ma, Y., Qi, L. S. 2024

  View details for DOI 10.1038/s41589-024-01645-x

  View details for PubMedID 38872012

  View details for PubMedCentralID 9508844

• Tuning Methylation-Dependent Silencing Dynamics by Synthetic Modulation of CpG Density. ACS synthetic biology Ma, Y., Budde, M. W., Zhu, J., Elowitz, M. B. 2023

  Abstract

  Methylation of cytosines in CG dinucleotides (CpGs) within promoters has been shown to lead to gene silencing in mammals in natural contexts. Recently, engineered recruitment of methyltransferases (DNMTs) at specific loci was shown to be sufficient to silence synthetic and endogenous gene expression through this mechanism. A critical parameter for DNA methylation-based silencing is the distribution of CpGs within the target promoter. However, how the number or density of CpGs in the target promoter affects the dynamics of silencing by DNMT recruitment has remained unclear. Here, we constructed a library of promoters with systematically varying CpG content, and analyzed the rate of silencing in response to recruitment of DNMT. We observed a tight correlation between silencing rate and CpG content. Further, methylation-specific analysis revealed a constant accumulation rate of methylation at the promoter after DNMT recruitment. We identified a single CpG site between TATA box and transcription start site (TSS) that accounted for a substantial part of the difference in silencing rates between promoters with differing CpG content, indicating that certain residues play disproportionate roles in controlling silencing. Together, these results provide a library of promoters for synthetic epigenetic and gene regulation applications, as well as insights into the regulatory link between CpG content and silencing rate.

  View details for DOI 10.1021/acssynbio.3c00078

  View details for PubMedID 37572041

• Tuning methylation-dependent silencing dynamics by synthetic modulation of CpG density. bioRxiv : the preprint server for biology Ma, Y., Budde, M. W., Zhu, J., Elowitz, M. B. 2023

  Abstract

  Methylation of cytosines in CG dinucleotides (CpGs) within promoters has been shown to lead to gene silencing in mammals in natural contexts. Recently, engineered recruitment of methyltransferases (DNMTs) at specific loci was shown to be sufficient to silence synthetic and endogenous gene expression through this mechanism. A critical parameter for DNA methylation-based silencing is the distribution of CpGs within the target promoter. However, how the number or density of CpGs in the target promoter affects the dynamics of silencing by DNMT recruitment has remained unclear. Here we constructed a library of promoters with systematically varying CpG content, and analyzed the rate of silencing in response to recruitment of DNMT. We observed a tight correlation between silencing rate and CpG content. Further, methylation-specific analysis revealed a constant accumulation rate of methylation at the promoter after DNMT recruitment. We identified a single CpG site between TATA box and transcription start site (TSS) that accounted for a substantial part of the difference in silencing rates between promoters with differing CpG content, indicating that certain residues play disproportionate roles in controlling silencing. Together, these results provide a library of promoters for synthetic epigenetic and gene regulation applications, as well as insights into the regulatory link between CpG content and silencing rate.

  View details for DOI 10.1101/2023.05.30.542205

  View details for PubMedID 37398290

  View details for PubMedCentralID PMC10312471

• Synthetic mammalian signaling circuits for robust cell population control. Cell Ma, Y., Budde, M. W., Mayalu, M. N., Zhu, J., Lu, A. C., Murray, R. M., Elowitz, M. B. 2022

  Abstract

  In multicellular organisms, cells actively sense and control their own population density. Synthetic mammalian quorum-sensing circuits could provide insight into principles of population control and extend cell therapies. However, a key challenge is reducing their inherent sensitivity to "cheater" mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. We designed a paradoxical population control circuit, termed "Paradaux," in which auxin stimulates and inhibits net cell growth at different concentrations. This circuit limited population size over extended timescales of up to 42days of continuous culture. By contrast, when operating in a non-paradoxical regime, population control became more susceptible to mutational escape. These results establish auxin as a versatile "private" communication system and demonstrate that paradoxical circuit architectures can provide robust population control.

  View details for DOI 10.1016/j.cell.2022.01.026

  View details for PubMedID 35235768