Regeneration of many cell types found in adult organs relies upon the presence of relatively small pools of undifferentiated stem cells. Initial studies that attempted to isolate stem cells and propagate them in vitro have been complemented by analysis of stem cells in their endogenous tissues where they are subject to a variety of regulatory cues. This has been facilitated by the advent of new methods for lineage tracing and genetic manipulation of stem cells and their associated niche cells. The picture that is emerging is that different stem cell populations utilize diverse processes to ensure maintenance of the stem cell pool accompanied by production of cells committed to regenerate differentiated cells.

As life expectancy rises, the prevalence of heart failure is steadily increasing, while donors for organ transplantation remain in short supply (Zwi-Dantsis and Gepstein, 2012). Indeed, myocardial infarction represents the foremost cause of death within industrialized nations (Henning, 2011) and further, approximately 1% of all newborns harbor a congenital heart defect. Although medical interventions allow>80% of those with cardiac defects to survive to adulthood, there are often extreme emotional and financial burdens that accompany such congenital anomalies, and many individuals will remain at a heightened risk for myocardial infarction throughout the remainder of their lives (Verheugt et al., 2010; Amianto et al., 2011). In this review, we will discuss the nature of the failing heart and strategies for repair from an epigenetic standpoint. Significant focus will reside on pluripotent-to-cardiomyocyte differentiation for cell replacement, epigenetic mechanisms of cardiomyocyte differentiation, epigenetic “memories,” and epigenetic control of cardiomyocyte cell fate toward translational utility.

Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum (ER), the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response (UPR). Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR–ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.

Renal failure is a medical condition in which the kidneys are not working properly. There are two types of kidney failure: 1) acute kidney failure, which is sudden and often reversible with adequate treatment; and 2) chronic renal failure, which develops slowly and often is not reversible. The last stage of chronic renal failure is fatal without dialysis or kidney transplant. The treatment for chronic renal failure is focusing on slowing the progression of kidney damage. Several reports have described a promising approach to slow the loss of renal function through inhibition of the basolateral membrane, Ca²⁺-activated K⁺ (KCa3.1) channel with a selective and nontoxic blocker TRAM-34. This review summarizes pathophysiological studies that describe the role of KCa3.1 in kidney diseases.

Vertebrates have evolved a powerful vascular system that involves close interactions between blood vessels and target tissues. Vascular biology had been mostly focused on the study of blood vessels for decades, which has generated large bodies of knowledge on vascular cell development, function and pathology. We argue that the prime time has arrived for vascular research on vessel-tissue interactions, especially target tissue regulation of vessel development. The central nervous system (CNS) requires a highly efficient vascular system for oxygen and nutrient transport as well as waste disposal. Therefore, neurovascular interaction is an excellent entry point to understanding target tissue regulation of blood vessel development. In this review, we summarize signaling pathways that transmit information from neural cells to blood vessels during development and the mechanisms by which they regulate each step of CNS angiogenesis. We also review important mechanisms of neural regulation of blood-brain barrier establishment and maturation, highlighting different functions of neural progenitor cells and pericytes. Finally, we evaluate potential contribution of malfunctioning neurovascular signaling to the development of brain vascular diseases and discuss how neurovascular interactions could be involved in brain tumor angiogenesis.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter (<1 kb upstream from the transcription start site) is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these elements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority. In this study, we align TH proximal promoter nucleotide sequences from several vertebrate species to identify evolutionarily conserved motifs. This analysis identified three elements (a TATA box, cyclic AMP response element (CRE) and a 5′-GGTGG-3′ site) that constitute the core of an ancient vertebrate TH promoter. Focusing on only eutherian mammals, two regions of high conservation within the proximal promoter were identified: a ~250 bp region adjacent to the transcription start site and a ~85 bp region located approximately 350 bp further upstream. Within both regions, conservation of previously reported cis-regulatory motifs and human single nucleotide variants was evaluated. Transcription reporter assays in a TH -expressing cell line demonstrated the functionality of highly conserved motifs in the proximal promoter regions and electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding (CREB) protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cis-regulatory motifs that underlie a core set of regulatory mechanisms in mammals.

With the rapid development of nanotechnology, nanomaterials have been used in numerous fields. However, these nanomaterials could also result in risk for human and environmental health. To make a comparison of the health effects of three different kinds of nanomaterials, 28 male BALB/c mice were randomly divided into four groups. Three experimental groups were exposed to different kinds of nanomaterials including graphene, graphene oxide and single wall carbon nanotubes (SWCNTs) by intraperitoneal injection while the control group received a saline injection. The exposure dose of experimental groups was 4mg/kg. After seven days, sections of mice kidney were taken, the organ coefficient of both kidney and brain was counted, and the reactive oxygen species (ROS) level, glutathione (GSH) and malondialdehyde (MDA) content was measured. Our results showed that in the experimental groups, the organ coefficient and GSH content in mice kidneys and brains decreased, whereas the ROS level and MDA content increased, when compared with the control. The graphene oxide group was statistically significant (p<0.05), while the SWCNTs group had extremely significant difference (p<0.01). Morphological changes in the kidney were also seen in the experimental groups. These results demonstrate that oxidative damage to mice kidneys and brains induced by SWCNTs and graphene oxide is more severe than graphene. The degree of damage caused by these three typical nanomaterials is different, probably due to several parameters including particle size, surface character, and shape.