Project description:We previously identified functional distinct sub-populations in adult male gWAT Pdgfrb+ cells utilizing the MuralChaser lineage tracking system and single-cell RNA-seq. Later in this related submission, we performed single-cell RNA-seqs on different developing stage of gWAT (P3, P7 and 5-week). We identified 4 sub-populations of Pdgfrb+ cells. Bulk-mRNA were conducted to these sub-populations in order to understand their transcriptomic profiles.
Project description:We previously identified functional distinct sub-popultions in adult male gWAT Pdgfrb+ cells utilizing the MuralChaser lineage tracking system and Single-cell RNA-seq. To examine the cellular altas and developmental aspects of male gWAT, we performed Single-cell RNA-seqs on different developing stage of gWAT (P3,P7 and 5-week). To examine the mesothelial origin hypothesis of gWAT, we also performed Single-cell RNA-seq on P7 gWAT associated mesothelial cells.
Project description:White adipose tissue regulates metabolism; the importance of this control is highlighted by the ongoing pandemic of obesity and associated complications such as diabetes, atherosclerosis, and cancer. White adipose tissue maintenance is a dynamic process, very little is known about how pharmacologic stimuli affect such plasticity. Combining in vivo lineage marking and BrdU labeling strategies, we found that rosiglitazone, a member of the thiazolidinedione class of glucose-lowering medicines, markedly increases the evolution of adipose progenitors into adipocytes. Notably, chronic rosiglitazone administration disrupts the adipogenic and self-renewal capacities of the stem cell compartment and alters its molecular characteristics. These data unravel unknown aspects of adipose dynamics and provide a basis to manipulate the adipose lineage for therapeutic ends. The goal of this gene expression array was to identify changes in molecular expression in adipose progenitors isolated from mice that underwent two-month rosiglitazone treatment. Adipose SV GFP+ cells (adipose progenitors) were FACS-isolated from adult AdipoTrak mice that had been treated with or without rosiglitazone (0.0075%) for 2 months. RNAs isolated from these cells were used for microarray. Each cohort contains 3-4 mice, each experimental group (-TZD and +TZD) contains 3 cohorts.
Project description:Adult white adipose tissue (WAT) harbors distinct mesenchymal stromal cell subpopulations that differentially affect WAT function and plasticity. Here we unveil the cellular landscape of the perinatal epididymal WAT primordium using single-cell transcriptomics in male mice. We reveal that adipocyte precursor cells and fibro-inflammatory progenitors (FIPs) emerge as functionally distinct PDGFRβ+ subpopulations within the epididymal WAT anlagen prior to adipocyte accrual. We further identify important molecular and functional differences between perinatal and adult FIPs, including differences in their pro-inflammatory response, adipogenic capacity and anti-adipogenic behavior. Notably, we find that transient overexpression of Pparg in PDGFRβ+ cells only during postnatal days 0.5 to 7.5 in male mice leads to hyperplastic WAT development, durable progenitor cell reprogramming, and protection against pathologic WAT remodeling and glucose intolerance in adult-onset obesity. Thus, factors that alter the adipogenic capacity of perinatal adipose progenitors can have long-lasting effects on progenitor plasticity, tissue expandability and metabolic health into adulthood.
Project description:White adipose tissue regulates metabolism; the importance of this control is highlighted by the ongoing pandemic of obesity and associated complications such as diabetes, atherosclerosis, and cancer. White adipose tissue maintenance is a dynamic process, very little is known about how pharmacologic stimuli affect such plasticity. Combining in vivo lineage marking and BrdU labeling strategies, we found that rosiglitazone, a member of the thiazolidinedione class of glucose-lowering medicines, markedly increases the evolution of adipose progenitors into adipocytes. Notably, chronic rosiglitazone administration disrupts the adipogenic and self-renewal capacities of the stem cell compartment and alters its molecular characteristics. These data unravel unknown aspects of adipose dynamics and provide a basis to manipulate the adipose lineage for therapeutic ends. The goal of this gene expression array was to identify changes in molecular expression in adipose progenitors isolated from mice that underwent two-month rosiglitazone treatment.
Project description:During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics were performed comparing the livers of yorkshire pigs at postnatal day seven and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins comparing neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1) and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), an enigmatic fifth hexokinase associated with glucose disturbances in pregnant women was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.