Contact

  • Work
    ananthg@stanford.edu
    University - Staff Department: Institute for Immunity, Transplantation, and Infection Operations Position: Senior Data Scientist

Additional Info

  • Mail Code: 5479

All Publications

  • Mass-cytometry-based quantitation of global histone post-translational modifications at single-cell resolution across peripheral immune cells in IBD. Journal of Crohn's & colitis Bai, L., Dermadi, D., Kalesinskas, L., Dvorak, M., Chang, S. E., Ganesan, A., Rubin, S. J., Kuo, A., Cheung, P., Donato, M., Utz, P. J., Habtezion, A., Khatri, P. 2022

    Abstract

    Current understanding of histone post-translational modifications (histone modifications) across immune cell types in patients with inflammatory bowel disease (IBD) during remission and flare is limited. The study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.We performed a case-control study of 94 subjects (83 IBD patients and 11 healthy controls). IBD patients had either UC (n=38) or CD (n=45) in clinical remission or flare. We used epigenetic profiling by time-of-flight (EpiTOF) to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients.We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34 + hematopoietic progenitors, and a subset of CD56 bright NK cells and γδ T cells characterized by distinct histone modifications associated with the gene transcription. The subset of CD56 bright NK cells had increased several histone acetylations. An epigenetically defined subset of NK was associated with higher levels of CRP in peripheral blood. CD14+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation.We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.

    View details for DOI 10.1093/ecco-jcc/jjac194

    View details for PubMedID 36571819