Biology subjects

Moller, A. F.

Publications and source records attributed to Moller, A. F..

3 recordsLinked to original sources

bioRxiv2025

Single cell-resolved transcriptional dynamics of human subcutaneous adipose tissue during lifestyle- and bariatric surgery-induced weight loss

During sustained weight gain, human white adipose tissue undergoes dramatic remodeling that may compromise adipose tissue function and lead to obesity comorbidities such as cardiometabolic disease. These comorbidities can be at least partially reversed by weight loss; however, the degree to which human adipose tissue is remodeled during weight loss is currently unclear. Here, we have used snRNA-seq combined with bulk RNA-seq and 3D light microscopy to investigate the cellular and transcriptional alterations in abdominal subcutaneous adipose tissue (ASAT) from a unique cohort of obese individuals undergoing initially modest (8-10%) lifestyle-induced weight loss followed by a more dramatic (20-45%) bariatric surgery-induced weight loss. We show that in response to this weight loss, ASAT in both males and females underwent dramatic compositional and transcriptional remodeling. Most notably, surgery-indued weight loss led to an increase in the adipose vascular compartment, a dramatic reduction in proinflammatory immune cells, and a tissue-wide reduction in inflammatory gene signatures. In response to modest weight loss, we observed an increase in specific progenitor populations and an induction of proadipogenic genes, indicating that this process is important for the early adaptation of AT to weight loss that might contribute to the early overall beneficial effects on insulin sensitivity and systemic inflammation.

cell biology↗

bioRxiv2023

A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals non-hierarchical model of development

The specialized cell-types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell-fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying novel, multipotent early epithelial progenitors that execute multi-lineage cues before specialising into late-stage ionocytes, goblet and basal cells. Combining in silico lineage inference, in situ hybridization and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors, chart cell- type emergence and fate progression into specialized cell-types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programmes across vertebrates. We uncover a continuous non-hierarchical model of MCE development alongside a significant data resource for understanding respiratory biology.

developmental biology↗

bioRxiv2020

Predicting gene regulatory networks from cell atlases

Recent single-cell RNA-sequencing atlases have surveyed and identified major cell-types across different mouse tissues. Here, we computationally reconstruct gene regulatory networks from 3 major mouse cell atlases to capture functional regulators critical for cell identity, while accounting for a variety of technical differences including sampled tissues, sequencing depth and author assigned cell-type labels. Extracting the regulatory crosstalk from mouse atlases, we identify and distinguish global regulons active in multiple cell-types from specialised cell-type specific regulons. We demonstrate that regulon activities accurately distinguish individual cell types, despite differences between individual atlases. We generate an integrated network that further uncovers regulon modules with coordinated activities critical for cell-types, and validate modules using available experimental data. Inferring regulatory networks during myeloid differentiation from wildtype and Irf8 KO cells, we uncover functional contribution of Irf8 regulon activity and composition towards monocyte lineage. Our analysis provides an avenue to further extract and integrate the regulatory crosstalk from single-cell expression data. SummaryIntegrated single-cell gene regulatory network from three mouse cell atlases captures global and cell-type specific regulatory modules and crosstalk, important for cellular identity.

bioinformatics↗