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Little is known about genes that induce stem cells differentiation into astrocytes. We previously described that heat shock protein 27 (HSP27) downregulation is directly related to neural differentiation under chemical induction in placenta-derived multipotent stem cells (PDMCs). Using this neural differentiation cell model, we cross-compared transcriptomic and proteomic data and selected 26 candidate genes with the same expression trends in both omics analyses. Those genes were further compared with a transcriptomic database derived from Alzheimer's disease (AD). Eighteen out of 26 candidates showed opposite expression trends between our data and the AD database. The mRNA and protein expression levels of those candidates showed downregulation of HSP27, S100 calcium-binding protein A16 (S100A16) and two other genes in our neural differentiation cell model. Silencing these four genes with various combinations showed that co-silencing HSP27 and S100A16 has stronger effects than other combinations for astrocyte differentiation. The induced astrocyte showed typical astrocytic star-shape and developed with ramified, stringy and filamentous processes as well as differentiated endfoot structures. Also, some of them connected with each other and formed continuous network. Immunofluorescence quantification of various neural markers indicated that HSP27 and S100A16 downregulation mainly drive PDMCs differentiation into astrocytes. Immunofluorescence and confocal microscopic images showed the classical star-like shape morphology and co-expression of crucial astrocyte markers in induced astrocytes, while electrophysiology and Ca2+ influx examination further confirmed their functional characteristics. In conclusion, co-silencing of S100A16 and HSP27 without chemical induction leads to PDMCs differentiation into functional astrocytes. [ABSTRACT FROM AUTHOR]

Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted. [ABSTRACT FROM AUTHOR]