Stra13 and Sharp-1, the non-grouchy regulators of development and disease.

Stra13 and Sharp-1 are transcriptional repressors that share domain structure similarity with members of the basic helix-loop-helix-Orange subfamily. In contrast to other members that include Hes and Hey proteins, transcriptional repression mediated by Stra13 and Sharp-1 does not involve recruitment of the corepressor Groucho. Both proteins undergo sumoylation at evolutionarily conserved sites, and this posttranslational modification serves as a platform for association with chromatin-modifying enzymes including histone deacetylases and histone methyltransferases. In addition to being widely expressed during embryonic development and in adult tissues, the expression of both genes is induced by a number of stimuli. Loss-of-function and gain-of-function studies have demonstrated their function in cellular differentiation and regeneration, in regulation of circadian rhythms, immune homeostasis, and metabolism. Given their diverse physiological functions in several tissues, it is not surprising that deregulated expression of Stra13 and Sharp-1 is apparent in human pathologies. Here, we review our current understanding of their cellular functions that suggest a requirement in maintenance of tissue homeostasis.

G9a, a multipotent regulator of gene expression.

Lysine methylation of histone and non-histone substrates by the methyltransferase G9a is mostly associated with transcriptional repression. Recent studies, however, have highlighted its role as an activator of gene expression through mechanisms that are independent of its methyltransferase activity. Here we review the growing repertoire of molecular mechanisms and substrates through which G9a regulates gene expression. We also discuss emerging evidence for its wide-ranging functions in development, pluripotency, cellular differentiation and cell cycle regulation that underscore the complexity of its functions. The deregulated expression of G9a in cancers and other human pathologies suggests that it may be a viable therapeutic target in various diseases.

Long-term expansion and pluripotent marker array analysis of Wharton's jelly-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) with their multilineage developmental plasticity comprise a promising tool for regenerative cell-based therapy. Despite important biological properties, which the MSCs from different sources share, the differences between them are poorly understood. Hence, it is required to assign a molecular signature to each of these MSC populations, based on stem cell related genes and early lineage or developmental markers. Understanding their propensity to differentiate to different lineages is fundamental for the development of successful cell-based therapies. Culture expansion of MSCs is a prerequisite, since high absolute numbers of stem cells are required to attain a clinical dose. Here, we compared the different culture conditions for long-term expansion of human MSCs isolated from the Wharton's jelly (WJ) of the umbilical cord while preserving their stem cell characteristics and differentiation potential. We find that DMEM-KO and DMEM-F12 are superior as compared to the other media tested in supporting the in vitro expansion of the WJ-MSCs. We studied the gene expression profile of WJ and bone marrow-derived MSCs (BM-MSCs) both at early and late passages using Human Stem Cell Pluripotency Array, and our data revealed differences at the transcriptional level between the two MSC types. Compared to BM-MSCs, WJ-MSCs had higher expression of undifferentiated human embryonic stem cell (hES) markers like NANOG, DNMT3B, and GABRB3, pluripotent/stem cell markers, as well as some early endodermal markers both at early and late passages. To conclude, WJ-MSCs possess properties of true stem cells, which they retain even after extended in vitro culturing.