The utility of stem cells in pediatric urinary bladder regeneration.

Pediatric patients with a neurogenic urinary bladder, caused by developmental abnormalities including spina bifida, exhibit chronic urological problems. Surgical management in the form of enterocystoplasty is used to enlarge the bladder, but is associated with significant clinical complications. Thus, alternative methods to enterocystoplasty have been explored through the incorporation of stem cells with tissue engineering strategies. Within the context of this review, we will examine the use of bone marrow stem cells and induced pluripotent stem cells (iPSCs), as they relate to bladder regeneration at the anatomic and molecular levels. The use of bone marrow stem cells has demonstrated significant advances in bladder tissue regeneration as multiple aspects of bladder tissue have been recapitulated including the urothelium, bladder smooth muscle, vasculature, and peripheral nerves. iPSCs, on the other hand, have been well characterized and used in multiple tissue-regenerative settings, yet iPSC research is still in its infancy with regards to bladder tissue regeneration with recent studies describing the differentiation of iPSCs to the bladder urothelium. Finally, we examine the role of the Sonic Hedgehog signaling cascade that mediates the proliferative response during regeneration between bladder smooth muscle and urothelium. Taken together, this review provides a current, comprehensive perspective on bladder regeneration.

Genome-wide quantitative assessment of variation in DNA methylation patterns.

Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.