Biomedical subjects

Saravanan Ganesan

Publications and source records attributed to Saravanan Ganesan.

2 recordsLinked to original sources

PubMed2026

Type 1 interferon perturbates clonal competition by reshaping human blood development.

Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα effects on mutated stem cells from the admixed wild-type HSCs, with respect to their differentiation, transcriptomes, immunophenotypes and chromatin accessibility. IFNα simultaneously activated HSCs into two polarized states: a lymphoid progenitor expansion associated with an anti-inflammatory state and an inflammatory myeloid progenitor state derived from HSCs. The augmented lymphoid differentiation balanced the typical myeloproliferative-neoplasm-induced myeloid bias, associated with normalized blood counts. Somatic mutations modified the effects of IFNα on HSC differentiation and cell cycle entry rates. Clonal fitness upon IFNα exposure was due to resistance of CALR- or JAK2-mutated stem cells to differentiate into inflammatory myeloid progenitors.

Journal Article↗

PubMed2026

Single-cell mapping of regulatory DNA-protein interactions.

Gene expression is controlled by transcription factors (TFs), whose genome binding is shaped by chromatin accessibility and histone modifications, yet mapping these interactions, particularly those with weak affinity or a transient nature, in single cells remains technically challenging. To address this gap, we developed docking and deamination followed by sequencing (D&D-seq), a single-cell immuno-tethering technology for profiling DNA-protein interactions. D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil editing at protein-bound genomic sites. This approach is compatible with standard single-cell multi-omic workflows and therefore allows integrated analyses of gene regulation. Using assay for transposase-accessible chromatin using sequencing (ATAC-seq) and single-cell ATAC-seq (scATAC-seq), we assessed chromatin accessibility as a functional readout of TF activity, and by coupling D&D-seq with whole-genome sequencing, we captured CTCF binding in both active and inactive chromatin compartments.

Animals↗