PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages.

We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-beta signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-beta, PDGF, and beta-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

Detection of severe acute respiratory syndrome coronavirus in blood of infected patients.

Severe acute respiratory syndrome (SARS) has caused major outbreaks worldwide, resulting in an urgent need to obtain sensitive and accurate diagnosis of this disease. PCR-based detection methods were developed for use on a variety of samples, including blood. Eighteen subjects were investigated, and results indicated that blood samples contain sufficient virus for detection by using quantitative real-time PCR.

The response of murine macrophages to infection with Yersinia pestis as revealed by DNA microarray analysis.

Macrophages play a crucial role in recognition and phagocytosis of pathogens and in the induction of response, immunity and immunopathology. A key strategy employed by numerous pathogens such as Yersinia pestis is to circumvent the immune response of the host via actively down-regulating the activation of macrophages. The study on host-pathogen interaction and gene expression is imperative for the development of alternative therapeutics. We have combined Suppression Subtractive Hybridisation (SSH), Microarray techniques, Northern blot analysis and quantitative reverse transcription coupled PCR (RT-PCR) to gain a view of differential host gene expression in response to Y. pestis-26 degrees C infection. In our study, a total of 22 different genes were identified as up-regulated in response to the Y. pestis infection. These genes include unknown EST's, cytokines, enzyme of cytokine, receptors, ligands, transcriptional factors, inhibitor of transcriptional factor, and proteins involved with cytoskeleton. More interestingly, among them are 7 genes that encode for factors known to be associated with cell cycling and cell proliferation, with 3 of them playing a role in apoptosis. Our data also indicate that macrophage cells undergo apoptosis during an infection with Y. pestis-37 degrees C, however an infection with 26 degrees C cultures results in a delayed apoptosis. The correlation between the delayed apoptosis and the up-regulation of anti-apoptotic gene is currently being studied.