Patterns of Life
Advancing Spatial Omics for a Better Understanding of Metabolic Tissues
Time: Fri 2025-05-23 09.15
Video link: https://kth-se.zoom.us/j/65783126092
Language: English
Subject area: Biotechnology
Doctoral student: Nayanika Bhalla , Genteknologi, Science for Life Laboratory, SciLifeLab
Opponent: Professor Gonçalo Castelo-Branco, Karolinska Institutet
Supervisor: Universitetslektor Patrik Ståhl, Science for Life Laboratory, SciLifeLab, Genteknologi
QC 2025-04-28
Abstract
Life hinges on the precise interplay between gene regulation and metabolism, a dynamic balance that unfolds in specific tissues and underlies both normal physiology and disease. This thesis follows a unifying red thread, advancing spatial omics for tissue-specific metabolic insights and translational applications by combining cutting-edge spatial transcriptomics and spatial epigenomics to illuminate how local regulatory mechanisms shape metabolic function.
In the initial segment of the thesis, we establish the conceptual groundwork, exploring how chromatin accessibility and transcriptional programs orchestrate cellular metabolism. We then apply spatial transcriptomics to two distinct yet metabolically active tissues. Paper I maps subcutaneous white adipose tissue (WAT) and discovers multiple adipocyte subtypes with divergent insulin responses, underscoring the critical role of tissue architecture in metabolic homeostasis. Paper II extends these methods to the human placenta, revealing region-specific gene expression patterns that help explain the metabolic dysregulation observed in preeclampsia. Given the placenta’s pivotal role in maternal-foetal nutrient exchange, these findings offer novel insights into how morphological compartments become disrupted in disease.
Building on these insights, Paper III introduces spatial ATAC-seq, a novel technique for profiling open chromatin within intact tissues, linking regulatory elements to their spatial context. Paper IV refines this protocol for broader adoption, integrating it with commercial platforms and enabling seamless multi-omic workflows. Building on these technological advances, Paper V returns to adipose tissue in a clinically relevant setting, employing a multi-omic approach to chart the long-term remodelling of WAT after bariatric surgery. By capturing transcriptional shifts in adipocytes and immune–stromal interactions, we highlight the tissue-level transformations that underpin sustained metabolic improvements.
Collectively, these studies showcase how spatial omics can deepen our understanding of tissue-specific metabolism, bridging foundational biology and translational research. They also underscore the power of integrated multi-omic approaches in revealing how chromatin states, gene expression, and metabolic function intersect in situ. By decoding the spatial architecture of gene regulation, we not only unravel the cellular intricacies of adipose and placental tissues but also pave the way for targeted therapeutic interventions in metabolic diseases, offering a powerful lens through which to view, and ultimately shape human health.