Single-nucleus RNA sequencing reveals heterogeneity among multiple white adipose tissue depots

Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for comprehending its function and properties.However,existing single-nucleus RNA sequencing(snRNA-seq)studies of adipose tissue heterogeneity have examined only one or two depots.In this study,we employed snRNA-seq to test five representative depots including inguinal,epididymal,mesenteric,perirenal,and pericardial adipose tissues in mice under physiological conditions.By analyzing the contents of main cell catego-ries and gene profiles of various depots,we identified their distinctive physiological properties.Immune cells and fibro-adipogenic progenitor cells(FAPs)showed dramatic differences among WAT depots,while adipocytes seemed to be conserved.The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function.Moreover,the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis.Using a combination of RNA sequencing and snRNA-seq analysis,the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent.Our work estab-lishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.

Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death

Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

SPHINGOLIPIDOMIC AND CYCLOPEPTIDOMIC STUDIES ON CORDYCEPS

Cordyceps is a precious Chinese medicine with various pharmacological activities.In 1995,a potent immunosuppressive active sphingolipid named myriocin was isolated from the culture broth of Isaria sinclairii.FTY720,a sphingolipid analogue modified from myriocin,has been developed into an important oral drug for the treatment of multiple sclerosis and organ transplantation.