Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal.

In embryonic stem (ES) cells, a well-characterized transcriptional network promotes pluripotency and represses gene expression required for differentiation. In comparison, the transcriptional networks that promote differentiation of ES cells and the blastocyst inner cell mass are poorly understood. Here, we show that Sox17 is a transcriptional regulator of differentiation in these pluripotent cells. ES cells deficient in Sox17 fail to differentiate into extraembryonic cell types and maintain expression of pluripotency-associated transcription factors, including Oct4, Nanog, and Sox2. In contrast, forced expression of Sox17 down-regulates ES cell-associated gene expression and directly activates genes functioning in differentiation toward an extraembryonic endoderm cell fate. We show these effects of Sox17 on ES cell gene expression are mediated at least in part through a competition between Sox17 and Nanog for common DNA-binding sites. By elaborating the function of Sox17, our results provide insight into how the transcriptional network promoting ES cell self-renewal is interrupted, allowing cellular differentiation.

An Experience-Centered Approach to Training Effective Data Scientists.

Like medicine, psychology, or education, data science is fundamentally an applied discipline, with most students who receive advanced degrees in the field going on to work on practical problems. Unlike these disciplines, however, data science education remains heavily focused on theory and methods, and practical coursework typically revolves around cleaned or simplified data sets that have little analog in professional applications. We believe that the environment in which new data scientists are trained should more accurately reflect that in which they will eventually practice, and we propose here a data science master's degree program that takes inspiration from the residency model used in medicine. Students in the suggested program would spend their time working on a practical problem with an industry, government, or nonprofit partner, supplemented with coursework in data science methods and theory. We also discuss how this program can also be implemented in shorter formats to augment existing professional master's programs in different disciplines. This approach to learning by doing is designed to fill gaps in our current approach to data science education and ensure that students develop the skills they need to practice data science in a professional context and under the many constraints imposed by that context.

Capabilities of surface composition analysis using a long laser-induced breakdown spectroscopy spark.

An apparatus has been investigated based on laser-induced breakdown spectroscopy (LIBS) for the rapid determination of the spatial distribution of elements on surfaces. Cylindrical optics are used to create a linear spark approximately 1 cm in length. Light emitted by atoms excited along the spark is collected and provides a spatial profile of elemental composition in the sample when analyzed with a spectrometer and gated charge-coupled device (ICCD) detector. Moving the spark across the sample surface as spectral data is recorded at regularly spaced intervals allows for the development of a three-dimensional elemental distribution map (emission intensity versus spatial distribution across an area). An analysis of the spatial resolution of this methodology is presented along with representative data from several sample types. Application of full-image analysis allowing for simultaneous investigations into the spatial distributions of multiple elements is also discussed and results are presented.

Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons.

The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.

A transcriptional logic for nuclear reprogramming.

Limitations on a differentiated cell's pluripotency can be erased by nuclear transfer or by fusion with embryonic stem cells, but attempts to recapitulate this process of nuclear reprogramming by molecular means have failed. In this issue of Cell, Takahashi and Yamanaka (2006) take a rational approach to identifying a suite of embryonic transcription factors whose overexpression restores pluripotency to adult somatic cells.

Nanoscale pipetting for controlled chemistry in small arrayed water droplets using a double-barrel pipet.

We present a new methodology which provides for the miniaturization of one of the most common tools in use in chemistry and biology laboratories today-the micropipet. We have used glass-fabricated double-barrel nanopipets to controllably produce arrayed water droplets with volumes as small as a few attoliters under an organic layer. We have addressed individual droplets and added controlled amounts of either additional volume or reagents from one of the barrels of the pipet. We demonstrate that this method can be used for miniaturized cell-free protein expression.