Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo

Side population (SP) cells, which can be identified by their ability to exclude Hoechst 33342 dye, are one of the candidates for somatic stem cells. Although bone marrow SP cells are known to be long-term repopulating hematopoietic stem cells, there is little information about the characteristics of cardiac SP cells (CSPs). When cultured CSPs from neonatal rat hearts were treated with oxytocin or trichostatin A, some CSPs expressed cardiac-specific genes and proteins and showed spontaneous beating. When green fluorescent protein–positive CSPs were intravenously infused into adult rats, many more (∼12-fold) CSPs were migrated and homed in injured heart than in normal heart. CSPs in injured heart differentiated into cardiomyocytes, endothelial cells, or smooth muscle cells (4.4%, 6.7%, and 29% of total CSP-derived cells, respectively). These results suggest that CSPs are intrinsic cardiac stem cells and involved in the regeneration of diseased hearts

Survey of single-nucleotide polymorphisms in the gene encoding human deoxyribonuclease I-like 2 producing loss of function potentially implicated in the pathogenesis of parakeratosis

<div><p>Dysfunction of DNase I-like 2 (DNase 1L2) has been assumed to play a role in the etiology of parakeratosis through incomplete degradation of DNA in the epidermis. However, the pathogenetic background factor for such pathophysiologic conditions remains unknown. In this context, non-synonymous single-nucleotide polymorphisms (SNPs) in <i>DNASE1L2</i> that would potentially result in loss of <i>in vivo</i> DNase 1L2 activity might serve as a genetic risk factor for such pathophysiologic conditions. Our aim was to effectively survey the non-synonymous SNPs of <i>DNASE1L2</i> that would produce a loss-of-function variant of the enzyme together with a genetic distribution in the various populations. Here, the effects of all of the SNPs predicted by PolyPhen-2 analysis to be “probably damaging” (score = 1.000), and derived from frameshift/nonsense mutations, on the activity of DNase 1L2 were examined using the corresponding DNase 1L2 variants expressed in COS-7 cells. Genotyping of these SNPs was also performed in three ethnic groups including 14 different populations. Among the 28 SNPs examined, the minor allele of 23 SNPs was defined as a loss-of-function variant resulting in loss of DNase 1L2 function, indicating that Polyphen-2 analysis could be effective for surveys of at least non-synonymous SNPs resulting in loss of function. On the other hand, these minor alleles were not distributed worldwide, thereby avoiding any marked reduction of the enzyme activity in human populations. Furthermore, all of the 19 SNPs originating from frameshift/ nonsense mutations found in <i>DNASE1L2</i> resulted in loss of function of the enzyme. Thus, the present findings suggest that each of the minor alleles for these SNPs may serve as one of genetic risk factors for parakeratotic skin diseases such as psoriasis, even though they lack a worldwide genetic distribution.</p></div

Evaluation on a prediction^a of functional effect of non-synonymous SNPs^b in <i>DNASE1L2</i> by PolyPhen-2.

<p>Evaluation on a prediction<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175083#t001fn001" target="_blank">^a</a> of functional effect of non-synonymous SNPs<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175083#t001fn002" target="_blank">^b</a> in <i>DNASE1L2</i> by PolyPhen-2.</p