Stem cells are unique cell populations identified in a variety of normal tissues and some cancers. Maintenance of stem cell pools is essential for normal development, tissue homeostasis, and tumorigenesis. Recent studies have revealed that Polycomb repressive complexes (PRCs) play a central role in maintaining stem cells by repressing cellular senescence and differentiation. Here, we will review recent findings on dynamic composition of PRC complexes and sub-complexes, how PRCs are recruited to chromatin, and their functional roles in maintaining self-renewal of stem cells. Furthermore, we will discuss how PRCs, CpG islands (CGIs), the INK4A/ARF/INK4B locus, and developmental genes form a hierarchical regulatory axis that is utilized by a variety of stem cells to maintain their self-renewal and identities.
Direct reprogramming technology has emerged as an outstanding technique for the generation of induced pluripotent stem cells (iPSCs) and various specialized cells directly from somatic cells of different species. Reprogramming techniques conventionally use viral vectors encoding transcription factors to induce fate conversion. However, the introduction of transgenes limits the therapeutic applications of the reprogrammed cells. To overcome safety-related concerns, small molecules offer some advantages over the existing methods for the control of gene expression and induction of cell fate conversion. Technical advances in optimizing concentrations, durations, structures, and combinations of small molecules make chemical reprogramming a safe and feasible method. This review provides a concise overview of cutting-edge findings regarding chemical-only reprogramming as one of the integration-free approaches to iPSC generation.
In biology, we continue to appreciate the fact that the DNA sequence alone falls short when attempting to explain the intricate inheritance patterns for complex traits. This is particularly true for human disorders that appear to have simple genetic causes. The study of epigenetics, and the increased access to the epigenetic profiles of different tissues has begun to shed light on the genetic complexity of many basic biological processes, both physiological and pathological. Epigenetics refers to heritable changes in gene expression that are not due to alterations in the DNA sequence. Various mechanisms of epigenetic regulation exist, including DNA methylation and histone modification. The identification, and increased understanding of key players and mechanisms of epigenetic regulation have begun to provide significant insight into the underlying origins of various human genetic disorders. One such disorder is CHARGE syndrome (OMIM 214800), which is a leading cause of deaf-blindness worldwide. A majority of CHARGE syndrome cases are caused by haploinsufficiency for the CHD7 gene, which encodes an ATP-dependent chromatin remodeling protein involved in the epigenetic regulation of gene expression. The CHD7 protein has been highly conserved throughout evolution, and research into the function of CHD7 homologs in multiple model systems has increased our understanding of this family of proteins, and epigenetic mechanisms in general. Here we provide a review of CHARGE syndrome, and discuss the epigenetic functions of CHD7 in humans and CHD7 homologs in model organisms.
Various Drosophila models of human disease have recently received increased interest. The main goal is to uncover the fundamental biological basis for human pathology taking advantage of the power of Drosophila genetics. This review examines a set of Drosophila seizure-sensitive mutations that model human seizure disorders, especially epilepsy. Also described is a novel set of mutations that act as seizure-suppressors that ameliorate epilepsy phenotypes in double mutant combinations.
Recent advances in fluorescence microscopy have provided researchers with powerful new tools to visualize cellular processes occurring in real time, giving researchers an unprecedented opportunity to address many biological questions that were previously inaccessible. With respect to neurobiology, these real-time imaging techniques have deepened our understanding of molecular and cellular processes, including the movement and dynamics of single proteins and organelles in living cells. In this review, we summarize recent advances in the field of real-time imaging of single synaptic vesicles in live neurons.
Cells contain a large number of metalloproteins that commonly harbor at least one metal ion cofactor. In metalloproteins, metal ions are usually coordinated by oxygen, sulfur, or nitrogen centers belonging to amino acid residues in the protein. The presence of the metal ion in metalloproteins allows them to take part in diverse biological processes, such as genome stability, metabolic catalysis, and cell cycle progression. Clinically, alteration of the function of metalloproteins in mammals is genetically associated with diseases characterized by DNA damage and repair defects. The present review focuses on the current perspectives of metal ion homeostasis in different organisms and summarizes the most recent understanding on magnesium, copper, iron, and manganese-containing proteins and their functional involvement in the maintenance of genome stability.
In multicellular organisms, several biological processes control the rise and fall of life. Different cell types communicate and co-operate in response to different stimulus through cell to cell signaling and regulate biologic processes in the cell/organism. Signaling in multicellular organism has to be made very secretly so that only the target cell responds to the signal. Of all the biomolecules, nature chose mainly proteins for secret delivery of information both inside and outside the cell. During cell signaling, proteins physically interact and shake hands for transfer of secret information by a phenomenon called as protein – protein interactions (PPIs). In both, extra and intracellular signaling processes PPIs play a crucial role. PPIs involved in cellular signaling are the primary cause for cell proliferation, differentiation, movement, metabolism, death and various other biological processes not mentioned here. These secret handshakes are very specific for specific functions. Any alterations/malfunctions in particular PPIs results in diseased condition. An overview of signaling pathways and importance of PPIs in cellular function and possibilities of targeting PPIs for novel drug development are discussed in this review.
This study presents the first definitive anatomical description of the tongue and lingual papillae of the cattle-yak. Data on tongues from 12 healthy cattle-yaks were collected. The results show that five types of papillae were identifiable on the tongue surface of the cattle-yak. Among these, three types were mechanical papillae (filiform, conical, and lenticular), and two types were gustatory papillae (vallate and fungiform). Some morphological features of the cattle-yak tongue were similar to those of domestic ruminants, but the lingual prominence was higher and more developed. For example, more mechanical papillae were present and they were covered by a thicker, keratinized epithelium, the conical papillae possibly perform an immune function, the fungiform papillae have more mucus-secreting pores, and the sublingual glands were more developed. This research will provide a further and detailed source of morphological information about the cattle-yak that is currently lacking in species-specific studies on the morphology of the Bovidae family.