Transcriptional Analysis of Sepsis-Induced Activation and Damage of the Adrenal Endothelial Microvascular Cells.

Bacterial sepsis is a serious threat to the body homeostasis and is often associated with high mortality in non-coronary intensive stations. In order to survive sepsis, rapid activation of the hypothalamus-pituitary-adrenal gland axis and sympathomedullary system is necessary. In many patients with sepsis, the function of those two arms of the stress system is dysregulated with underlying mechanisms remaining unknown. In our previous experimental studies, we have demonstrated that LPS-induced systemic inflammation and CLP-induced peritonitis can result in adrenal gland damage. Histological and transcriptomic analysis revealed a potential involvement of the adrenal microvascular endothelium in this process. However, our knowledge about the function of adrenal microvascular cells during sepsis is scarce. In the present study, we have characterized transcriptomic alterations in isolated mouse adrenal microvascular endothelial cells induced by systemic administration of bacterial LPS. Our results revealed that LPS induced a distinct transcriptomic profile in the adrenal microvascular cells, including multiple genes regulating inflammation, activation of the coagulation cascade and vascular permeability. Activation of those genes may be potentially involved in the damage to the microvascular endothelium and altogether contribute to the sepsis-mediated adrenal dysregulation.

In Toto Imaging of Dynamic Osteoblast Behaviors in Regenerating Skeletal Bone.

Osteoblasts are matrix-depositing cells that can divide and heal bone injuries. Their deep-tissue location and the slow progression of bone regeneration challenge attempts to capture osteoblast behaviors in live tissue at high spatiotemporal resolution. Here, we have developed an imaging platform to monitor and quantify individual and collective behaviors of osteoblasts in adult zebrafish scales, skeletal body armor discs that regenerate rapidly after loss. Using a panel of transgenic lines that visualize and manipulate osteoblasts, we find that a founder pool of osteoblasts emerges through de novo differentiation within one day of scale plucking. These osteoblasts undergo division events that are largely uniform in frequency and orientation to establish a primordium. Osteoblast proliferation dynamics diversify across the primordium by two days after injury, with cell divisions focused near, and with orientations parallel to, the scale periphery, occurring coincident with dynamic localization of fgf20a gene expression. In posterior scale regions, cell elongation events initiate in areas soon occupied by mineralized grooves called radii, beginning approximately 2 days post injury, with patterned osteoblast death events accompanying maturation of these radii. By imaging at single-cell resolution, we detail acquisition of spatiotemporally distinct cell division, motility, and death dynamics within a founder osteoblast pool as bone regenerates.

The triumvirate of beta-cell regeneration: solutions and bottlenecks to curing diabetes.

On 11 January 1922 insulin injection was used for the first time in the treatment of diabetes. Even today, daily insulin injections are the life-saving treatment for patients with Type 1 diabetes and advanced Type 2 diabetes. However, insulin injections often fail to achieve full glucose control, which in the long-term leads to multiple complications and mortality. Beta-cells, the natural producers and secretors of insulin, remain the gold-standard in regulating blood glucose levels. In this review, we focus on three strategies aiming at counteracting beta-cell loss in order to gain insulin independence: replacement, replication and protection. The three approaches, together termed as the triumvirate of beta-cell regeneration, may constitute the basis for a future cure for diabetes.