In the context of the Center for Functional Genomics and Tissue Plasticity (ATLAS), the Mandrup Group investigates the plasticity of adipose tissue in response to obesity and weight loss. We apply single cell technologies combined with other functional genomics approaches to study the transcriptional networks and cellular crosstalk driving cellular plasticity of human adipose tissues; however, we also use models for mechanistic follow-up studies.

Single-nucleus RNA sequencing (snRNA-seq) analyses of mouse and human white adipose tissues by ATLAS and others have demonstrated several distinct subpopulations of the major cell types in human adipose tissues, i.e., adipocytes, fibro-adipo progenitors, and macrophages. Importantly, we and others have shown that the adipocyte and macrophage subpopulations undergo dramatic quantitative and qualitative changes during weight gain, and several lines of evidence indicate that this remodeling has major implications for adipose tissue adaptation as well as obesity pathology. We are investigating how the tissue architecture and intrinsic and extrinsic molecular signals drive cellular fate decisions and tissue plasticity during weight gain and to what extent these signals differ between depots. Furthermore, we investigate to what extent cellular and molecular signatures persist following weight loss.

This project is supported by grants from The Danish National Research Foundation, Sygeforsikringen "danmark", and The Novo Nordisk Foundation. 

People involved

	Babukrishna Maniyadath Postdoc
	Raquel Saborano Postdoc
	Rasmus Rydbirk Bioinformatics staff scientist
	Ellen Gammelmark PhD student
	Lukas mc Kenzie Oussoren PhD student
	Flora Berglund Fuglsang MSc student
	Luna Isabella Wassini Project student
	Alexander Hinz Project student

Relevant publications 

B. Maniyadath, Q. Zhang , R. K. Gupta, S. Mandrup (2023) Adipose tssue at single-cell resolution. Cell Metab. 35(3):386-413. doi: 10.1016/j.cmet.2023.02.002.

E. L. Van Hauwaert, E. Gammelmark, A. K. Sávári, L. Larsen, R. Nielsen, J. G. S. Madesen, S. Mandrup (2021) Isolation of nuclei from mouse white adipose tissue for single-nucleus genomics. STAR Protoc. Jun 17;2(3):100612. doi: 10.1016/j.xpro.2021.100612.

A. K. Sávári, E. L. Van Hauwaert, L. K. Markussen, E. Gammelmark, A-B. Marcher, M. F. Ebbesen, R. Nielsen, J. R. Brewer, J. G. S. Madsen, S. Mandrup (2021) Plasticity of Edididymal Adipose Tissue in Response to Diet-Induced Obesity at Single-Nucleus Resolution. Cell Metab. 33, 437-453. 

A. Rauch, A.K. Haakonsson, J.G.S. Madsen, M. Larsen, I. Forss, M.R. Madsen, E.L. Van Hauwaert, C. Wiwie, N.Z. Jespersen, M. Tencerova, R. Nielsen, B.D. Larsen, R. Röttger, J. Baumbach, C. Scheele, M. Kassem, S. Mandrup (2019) Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis. Nature Genetics 51, 716–727. 

J.G.S. Madsen*, A. Rauch*, E.L. Van Hauwaert, S.F. Schmidt, M. Winnefeld, S. Mandrup (2018) Integrated analysis of motif activity and gene expression changes of transcription factors. Genome Res. 28, 243-255.