Alladi Ramakrishnan Hall

Gene regulatory networks and cell-fate paradigms in health and diseases

Kedar N Natarajan

Technical University of Denmark

Single-cell and spatial transcriptomics has enabled profiling cell types, states from complex tissues, facilitating better understanding of human health and diseases.

I will present interdisciplinary experimental and computational efforts to investigate transcriptional regulation, gene regulatory networks and cell-fate paradigms. Firstly, using big-data single-cell atlases, we infer gene regulatory networks and causal drivers, acting across multiple cell types. I will highlight use cases in diseases, where regulatory activity better predicts perturbation and disease states. Secondly, by single-cell profiling of developing respiratory epithelium, we identify novel multipotent progenitors and chart its differentiation and lineage transitions into mature cell types (secretory, ciliated and basal cell types). Thirdly, I will present ongoing work on cell fitness and adversarial deep learning frameworks for cell type prediction.

Our work provides an avenue to further extract regulatory crosstalk from single-cell expression data and uncover cell fate paradigms in development.