Unveiling human white adipose tissue diversity at single-cell resolution

<p dir="ltr">Obesity is a growing global health concern, currently affecting over one billion individuals worldwide and significantly increasing the risk of cardiovascular, metabolic, and many other diseases. White adipose tissue (WAT), a highly heterogeneous and metabolically active organ, plays a central role in maintaining energy homeostasis and regulating the endocrine system. The distribution and cellular composition of WAT, which vary markedly among individuals and anatomical depots, are critical determinants of metabolic health. While recent single-cell technologies have advanced our understanding of WAT cytoarchitecture, current studies predominantly focus on subcutaneous and omental visceral fat, often overlooking the diversity within visceral depots. Furthermore, adipocytes present technical challenges for single-cell RNA sequencing due to their physical properties, prompting the use of single-nucleus RNA sequencing (snSeq), which introduces specific biases. Spatial transcriptomics (STx) offers an alternative approach, capturing transcriptomic information while preserving spatial context, albeit at a limited resolution. In this thesis, we integrated snSeq and STx data to investigate WAT heterogeneity in obesity. In <b>study I</b>, we identified novel adipocyte substates and associated one with insulin responsiveness. In <b>study II</b>, we systematically mapped WAT cell types across multiple datasets, linking cell-type composition to clinical traits. In <b>study III</b>, we examined spatial and cellular differences between intraperitoneal and subcutaneous depots, revealing depot-specific inflammatory signatures. Our findings underscore the significance of spatial and cellular context in adipose tissue, providing new insights into the molecular underpinnings of metabolic disease in obesity.</p><h3>List of scientific papers</h3><p dir="ltr">I. Backdahl J*, Franzen L*, Massier L, Li Q, <b>Jalkanen J,</b> Gao H, Andersson A, Bhalla N, Thorell A, Rydén M, Ståhl PL*, Mejhert N *. Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin. Cell Metab. 2021 Sep 7;33(9):1869-1882.e6. <a href="https://doi.org/10.1016/j.cmet.2021.07.018" rel="noreferrer noopener" target="_blank">https://doi.org/10.1016/j.cmet.2021.07.018</a></p><p dir="ltr">II. Massier L, <b>Jalkanen J,</b> Elmastas M, Zhong J, Wang T, Nono Nankam PA, Frendo-Cumbo S, Bäckdahl J, Subramanian N, Sekine T, Kerr AG, Tseng BTP, Laurencikiene J, Buggert M, Lourda M, Kublickiene K, Bhalla N, Andersson A, Valsesia A, Astrup A, Blaak EE, Ståhl PL, Viguerie N, Langin D, Wolfrum C, Blüher M, Rydén M*, Mejhert N *. An integrated single cell and spatial transcriptomic map of human white adipose tissue. Nat Commun. 2023 Mar 15;14(1):1438. <a href="https://doi.org/10.1038/s41467-023-36983-2" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41467-023-36983-2</a></p><p dir="ltr">III. <b>Jalkanen J*</b>, Zhong J*, Nono Nankam PA, Bhalla N, Elmastas M, Luo J, Weinbrenner S, Frendo-Cumbo S, Pesti B, Gourash W, Courcoulas A, Yang Loureiro Z, Dietrich A, Bäckdahl J, Buggert M, Kalucka J, Emont MP, Rosen ED, Blüher M, Kovacs P, Ståhl PL, Massier L, Rydén M*, Mejhert N *. Cytoarchitectural Profiling of White Adipose Tissue Depots Links Serum Amyloid A Expressing Adipocytes to Immune Cell Activation. [Submitted] </p><p dir="ltr">* These authors contributed equally</p>