Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4

Cell-secreted soluble factor signaling in a diffusion dominant microenvironment plays an important role on early stage differentiation of pluripotent stem cells invivo. In this study, we utilized a membrane-based two-chambered microbioreactor (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant microenvironment of the top chamber while providing enough nutrient through the bottom chamber. Speculating that accumulated FGF4 in the small top chamber will augment neuronal differentiation in the MB culture, we first differentiated mESCs for 8 days by using a chemically optimized culture medium for neuronal induction. However, comparison of cellular morphology and expression of neuronal markers in the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal differentiation in the MB culture. Therefore, to investigate whether microenvironment in the MB facilitates non-neuronal differentiation, we differentiated mESCs for 8 days by using chemically defined basal medium. In this case, differentiated cell morphology differed markedly between the MB and 6WP cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology in the 6WP. Expression of markers from the three germ layers indicated lower neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4 expression was remarkably upregulated in the MB culture. Inhibition of BMP4 signaling demonstrated that enhanced effect of upregulated BMP4 was responsible for the prominent meso- and endo-dermal differentiation in the MB. However, in the 6WP, downregulated BMP4 had a minimal influence on the differentiation behavior. Our study demonstrated utilization of a microbioreactor to modulate the effect of cell-secreted soluble factors by autoregulation and thereby inducing alternative self-capability of mESCs. Understanding and implementation of autoregulation of soluble factors similar to this study will lead to the development of robust culture systems to control ESC behavior.     

Bibliometric cartography of information retrieval research by using co-word analysis

The aim of this study is to map the intellectual structure of the field of Information Retrieval (IR) during the period of 1987–1997. Co-word analysis was employed to reveal patterns and trends in the IR field by measuring the association strengths of terms representative of relevant publications or other texts produced in IR field. Data were collected from Science Citation Index (SCI) and Social Science Citation Index (SSCI) for the period of 1987–1997. In addition to the keywords added by the SCI and SSCI databases, other important keywords were extracted from titles and abstracts manually. These keywords were further standardized using vocabulary control tools. In order to trace the dynamic changes of the IR field, the whole 11-year period was further separated into two consecutive periods: 1987–1991 and 1992–1997. The results show that the IR field has some established research themes and it also changes rapidly to embrace new themes.