Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

Abstract

Adipose browning has demonstrated therapeutic potentials in several diseases. Here, by conducting transcriptomic profiling at the single-cell and single-nucleus resolution, we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue (iWAT) at thermoneutrality or chronic cold condition. All major nonimmune cells within the iWAT, including adipose stem and progenitor cells (ASPCs), mature adipocytes, endothelial cells, Schwann cells, and smooth muscle cells, were recovered, allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling. Our findings also unravel the existence of subpopulations in mature adipocytes, ASPCs, and endothelial cells, as well as new insights on their interconversion and reprogramming in response to cold. The adipocyte subpopulation competent of major histocompatibility complex class II (MHCII) antigen presentation is potentiated. Furthermore, a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCII + adipocyte. Beige adipocytes are transdifferented from preexisting lipid generating adipocytes, which exhibit developmental trajectory from de novo differentiation of amphiregulin cells (Aregs). Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold. Our data reveal fundamental changes during cold-evoked adipose browning.

Network Meta-Analysis: Effect of Cold Stress on the Gene Expression of Swine Adipocytes ATGL, CIDEA, UCP2, and UCP3

“…Genes expressed in pig WAT include those involved in BAT differentiation in the natural growth state [29]. While there are no reports on pigs with BAT [30], pigs might possess beige (brite adipose tissue) [19], which could have a mutual-conversion relationship with WAT [5]. Our published articles indicate that cold stress can promote WAT browning [18].…”

“…Expression of certain adipocyte genes changes under cold stress conditions [5,16]. These genes are crucial in regulating the growth, differentiation, and function of adipocytes under cold stress.…”

“…Cold stress significantly affects gene expression in adipocytes [5]. Expression of cold stress-related genes regulates the growth, differentiation, and function of adipocytes, thereby affecting the balance of energy metabolism in the body.…”

“…Expression of cold stress-related genes regulates the growth, differentiation, and function of adipocytes, thereby affecting the balance of energy metabolism in the body. In addition, WAT browning has demonstrated therapeutic potential for the treatment of human diseases [5]. Further study of the influence of cold stress on adipocyte gene expression can help reveal the pathogeneses of obesity, insulin resistance, and other ailments [6], which will provide new insights into the treatment and prevention of these conditions [7].…”

Dissecting Spatiotemporal Structures in Spatial Transcriptomics via Diffusion-Based Adversarial Learning

“…Spatial transcriptomics (ST) technologies provides information of the spatial distribution of cells and gene expression [ 1 ]. Understanding the relative positioning of transcriptional expression within tissues is crucial for unraveling their spatial architectures and biological functions [ 2 , 3 ]. In recent years, the emerging spatial transcriptome sequencing technologies (e.g., 10X Visium [ 4 ], Spatial Transcriptomics [ 5 ], Slide-seq [ 6 ], Slide-seqV2 [ 7 ], HDST [ 8 ], seqFISH [ 9 , 10 ], seqFISH+ [ 11 ], MERFISH [ 12 , 13 ], and STARmap [ 14 ]) have facilitated the exploration of the intricate transcriptional architecture of heterogeneous tissues, prominently advancing our comprehension of the cellular mechanisms underlying various diseases [ 4 , 15 ].…”