Biology subjects

Emont, M. P.

Publications and source records attributed to Emont, M. P..

5 recordsLinked to original sources

bioRxiv2026

Single-Nuclear RNA Sequencing Reveals Regional Specialization and Cellular Interactions in Epicardial and Perivascular Adipose Tissue

Background: Adipose tissue surrounding the heart and vasculature plays critical roles in cardiovascular homeostasis and disease, yet the cellular and molecular milieu of these depots at single-cell resolution remains incompletely characterized. Understanding how regional adipocytes differ transcriptionally and communicate with neighboring cardiovascular cells is essential for developing targeted therapeutic strategies. Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on human adipose tissue from four anatomically distinct depots: ascending aorta, left atrium, right coronary artery, and subcutaneous fat. We characterized cellular composition, adipocyte and progenitor heterogeneity, depot-specific transcriptional programs, and intercellular communication networks. We further examined signaling remodeling in disease contexts, including atrial fibrillation and aortic aneurysm. Results: We identified six transcriptionally distinct adipocyte subpopulations and six adipocyte stromal and progenitor cell (ASPC) subpopulations were shared across depots but showed marked differences in abundance and gene expression reflecting developmental imprinting, including HOX family genes and anterior-posterior patterning programs. Intercellular communication analysis revealed depot-specific ligand-receptor interactions, with EPHA signaling identified as selectively enriched in the left atrial adipose depot. Disease-state analyses demonstrated extensive change in cell-cell communication in atrial fibrillation and aortic aneurysm, with differential regulation of FN1, EGF, SLIT, NOTCH, and CD46 signaling pathways. Conclusions: Our study reveals that cardiac and vascular adipose depots harbor transcriptionally specialized adipocytes and progenitors with distinct intercellular communication programs that are remodeled in atrial fibrillation and aortic aneurysm.

physiology↗

bioRxiv2026

Rapid Remodeling of Human White Adipose Tissue Following Bariatric Surgery

Bariatric surgery induces profound weight loss and improvement of obesity-associated metabolic dysfunction. Recent studies have shown that adipose tissue undergoes remodeling after weight loss, characterized by a reduction in proinflammatory immune cells, increased vascularization, and a shift in the adipocyte transcriptome, but these studies focused on time points long after surgery. We performed single nucleus RNA-seq (snRNA-seq) in subcutaneous white adipose tissue (SAT) samples from subjects with obesity undergoing bariatric surgery, collected at baseline and at one, six, and twelve months after surgery. We identify profound remodeling of SAT within the first month after surgery, characterized by a surge in lipid-associated macrophages and sharp reductions in specific populations of adipocytes, adipose stromal and progenitor cells (ASPCs), and endothelial cells. Transcriptional profiles strongly suggest that some adipocytes undergo apoptosis soon after surgery, while new adipocytes are generated by de novo differentiation. Mechanistically, the data are consistent with a model whereby coordinated early loss of a hedgehog signaling axis between endothelial cells and an anti-adipogenic population of ASPCs known as adipose regulatory cells (Aregs; ASPCPTCH2) enables a transient burst of adipogenesis to occur. Interestingly, very few of these early features seen in human subjects are represented in a mouse model of surgical weight loss.

physiology↗

bioRxiv2025

Single-nuclear transcriptomics of lymphedema-associated adipose reveals a pro-lymphangiogenic stromal cell population

Chronic lymphedema is a progressive, disfiguring disease that results from dysfunction of the lymphatic vasculature, causing distal accumulation of interstitial fluid, localized development of tissue edema, and expansion of subcutaneous adipose tissue (SAT). As the molecular mechanisms governing SAT remodeling in this disease are unclear, we performed single-nucleus RNA sequencing on paired control and affected SAT biopsies from patients with unilateral lymphedema. Lymphedema samples were characterized by expansion of SAA+ adipocytes, pro-adipogenic stem cells, and proliferation of lymphatic capillaries. A GRIA1+ lymphedema-enriched stromal cell population expressing VEGFC, ADAMTS3, and CCBE1 was identified, suggesting an enhanced axis of communication between adipose stem and progenitor cells (ASPCs) and lymphatic endothelial cells. Furthermore, lymphedema ASPC-conditioned media promoted lymphatic endothelial tube elongation and proliferation in vitro. These findings indicate a critical role for ASPCs in regulating adipocyte differentiation and lymphatic vascular remodeling in lymphedema, and provide a valuable resource for better understanding this disease.

cell biology↗

bioRxiv2024

Defining the Vascular Niche of Human Adipose Tissue Across Metabolic Conditions

IntroductionAdipose tissue homeostasis depends on a healthy vascular network. Vascular malfunction is a hallmark of obesity1, and vascular endothelial dysfunction, in particular, accelerates metabolic diseases, including obesity and diabetes. Single-cell transcriptomics studies have mapped the cellular landscape of human white adipose tissue (WAT)2-8. However, the vascular niche remains relatively undefined9, especially regarding its heterogeneity, function, and role in metabolic disease. To address this gap, we created a single-cell transcriptome atlas of human subcutaneous adipose tissue (SAT), comprising nearly 70,000 vascular cells from 65 individuals. We characterized seven canonical adipose tissue endothelial cell (AdEC) subtypes and identified a distinct heterogenous population, here referred to as sub-AdECs. Sub-AdECs exhibit gene signatures characteristic of multiple cell types, including mesenchymal, adipocytic, and immune, suggesting they possess diverse properties and identities. Through computational analyses and whole-mount imaging, we validated the occurrence of sub-AdECs and show that these cells likely arise through endothelial-mesenchymal transition (EndMT), the modulation of which limits obesity-associated adipose tissue inflammation and fibrosis. Furthermore, we compared the transcriptomes of vascular cells from individuals living with or without obesity and type 2 diabetes and find metabolic disease-associated inflammatory and fibrotic transcriptomic patterns. The atlas and accompanying analyses establish a solid foundation for investigations into the biology of the adipose tissue vascular niche and its contribution to the pathogenesis of metabolic disease.

cell biology↗

bioRxiv2021

A single cell atlas of human and mouse white adipose tissue

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense1. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D)2. Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

physiology↗