The molecular basis for ethnic variation and histological subtype differences in prostate cancer

Prostate cancer is a common malignancy among men in Western countries. Recently the morbidity and mortality of prostate cancer increase dramatically in several oriental countries including China. Rapidly evolving technology in molecular biology such as high-throughput sequencing and integrative analysis of genomic and transcriptomic landscapes have enabled the identification of key oncogenic events for prostate cancer initiation, progression and resistance to hormonal therapy. These surging data of prostate cancer genome also provide insights on ethnic variation and the differences in histological subtype of this disease. In this review, differences in the incidence of prostate cancer and the prevalence of main genetic alterations between Asian and Western populations are discussed. We also review the recent findings on the mechanisms underlying neuroendocrine differentiation of prostate cancer and the development of small cell neuroendocrine carcinoma after androgen deprivation therapy.

High-throughput physical phenotyping of cell differentiation

In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters.Parameters extracted from videos include size,deformability,deformation kinetics,and morphology.We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells,mesenchymal stem cells,neural stem cells,and their derivatives compared to size and deformability alone.In addition,we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation.This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner.Ultimately,such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.

星形胶质细胞之间的接触和生长因子信号传导的正反馈回路对星形胶质细胞成熟的调节

星形胶质细胞对于中枢神经系统的发育和功能至关重要。在大脑发育过程中,未成熟的星形胶质细胞会发生形态、分子、细胞和功能的变化以至成熟。尽管已经广泛研究了调节中枢神经系统中其他主要细胞类型(如神经元和少突胶质细胞)成熟过程的机制,但对于控制星形胶质细胞成熟的细胞和分子机制知之甚少。本研究确定了星形胶质细胞成熟的分子标志物,并建立了研究星形胶质细胞成熟机制的离体检验方法。离体条件下,成熟的星形胶质细胞表现出与在体星形胶质细胞相似的分子变化及类似的多种分子亚型。使用该系统,我们发现星形胶质细胞之间的接触强烈促进星形胶质细胞的成熟。此外,来自小胶质细胞、少突胶质细胞前体细胞或内皮细胞的分泌信号影响星形胶质细胞的一小部分基因,但不会持续改变星形胶质细胞的成熟。为了确定星形胶质细胞成熟的分子机制,我们用影响肿瘤相关基因功能的分子处理了成熟中的星形胶质细胞。我们发现肝素结合表皮生长因子样生长因子(HBEGF)和表皮生长因子受体(EGFR)信号通路的正反馈回路调节星形胶质细胞的成熟。此外,HBEGF、EGFR和肿瘤蛋白53(TP53)影响一些基因的表达,这些基因对纤毛发育,昼夜节律和突触功能至关重要。这些结果揭示了星形胶质细胞成熟的细胞和分子机制,对理解胶质母细胞瘤具有重要意义。