Mesodermal fate decisions of a stem cell: the Wnt switch

Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis.     

Development of DNA probes for cytotoxin and enterotoxin genes in enteric bacteria

DNA probes to identify the genes encoding toxins in enteric bacteria have been developed. Use of these probes reduces the number of animals required for toxicity testing, as suspect bacteria can be directly tested for the presence of toxin. We have augmented the gene probes available by developing probes against the Escherichia coli enterotoxin LTII and shiga toxin from Shigella dysenteriae 1. The LTII gene from E. coli 357900 was identified and characterised and a suitable internal probe was obtained. The LTII gene was found not to be common among enterobacteriae from various geographical locations. Isolates predominately of animal origin from Nigeria and Thailand hybridized with the probe. The shiga toxin gene was isolated from S. dysenteriae 1 by a combination of in vivo and in vitro methods. An internal probe was identified and used against different serogroups of Shigella and E. coli isolates. The probe was found to hybridize with S. dysenteriae 1 isolates and also some S. flexneri and S. sonnei strains. Representatives were tested for toxin production and found to produce toxin at low levels.     

Development of DNA probes for cytotoxin and enterotoxin genes in enteric bacteria

Summary DNA probes to identify the genes encoding toxins in enteric bacteria have been developed. Use of these probes reduces the number of animals required for toxicity testing, as suspect bacteria can be directly tested for the presence of toxin. We have augmented the gene probes available by developing probes against theEscherichia coli enterotoxin LTII and shiga toxin fromShigella dysenteriae 1.The LTII gene fromE. coli 357900 was identified and characterised and a suitable internal probe was obtained. The LTII gene was found not to be common among enterobacteriae from various geographical locations. Isolates predominately of animal origin from Nigeria and Thailand hybridized with the probe.The shiga toxin gene was isolated fromS. dysenteriae 1 by a combination of in vivo and in vitro methods. An internal probe was identified and used against different serogroups ofShigella andE. coli isolated. The probe was found to hybridize withS. dysenteriae 1 isolates and also someS. flexneri andS. sonnei strains. Representatives were tested for toxin production and found to produce toxin at low levels.     

Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes

Melanocytes and Schwann cells are derived from the multipotent population of neural crest cells. Although both cell types were thought to be generated through completely distinct pathways and molecular processes, a recent study has revealed that these different cell types are intimately interconnected far beyond previously postulated limits in that they share a common post-neural crest progenitor, i.e. the Schwann cell precursor. This finding raises interesting questions about the lineage relationships of hitherto unrelated cell types such as melanocytes and Schwann cells, and may provide clinical insights into mechanisms of pigmentation disorders and for cancer involving Schwann cells and melanocytes.     

Home sweet home: skin stem cell niches

The epidermis and its appendages, such as the hair follicle (HF), continually regenerate throughout postnatal mammalian life due to the activity of resident epithelial stem cells (SCs). The follicular SC niche, or the bulge, is composed of a heterogeneous population of self-renewing multipotent cells. Multiple intrinsic molecular mechanisms promote the transition of follicular SCs from quiescence to activation. In addition, numerous extrinsic cell types influence the activity and characteristics of bulge cells. Ultimately, the balance between these intrinsic and extrinsic mechanisms influences the function of bulge cells during homeostasis and tissue regeneration and likely contributes to skin tumorigenesis. Here, we review both the intrinsic and extrinsic factors that contribute to the skin SC niche.     

Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research

Cancer stem cells have been hypothesized to drive the growth and metastasis of tumors. Because they need to be targeted for cancer treatment, they have been isolated from many solid cancers. However, cancer stem cells from primary human gastric cancer tissues have not been isolated as yet. For the isolation, we used two cell surface markers: the epithelial cell adhesion molecule (EpCAM) and CD44. When analyzed by flow cytometry, the EpCAM⁺/CD44⁺ population accounts for 4.5% of tumor cells. EpCAM⁺/CD44⁺ gastric cancer cells formed tumors in immunocompromised mice; however, EpCAM^?/CD44^?, EpCAM⁺/CD44^? and EpCAM^?/CD44⁺ cells failed to do so. Xenografts of EpCAM⁺/CD44⁺ gastric cancer cells maintained a differentiated phenotype and reproduced the morphological and phenotypical heterogeneity of the original gastric tumor tissues. The tumorigenic subpopulation was serially passaged for several generations without significant phenotypic alterations. Moreover, EpCAM⁺/CD44⁺, but not EpCAM^?/CD44^?, EpCAM⁺/CD44^? or EpCAM^?/CD44⁺ cells grew exponentially in vitro as cancer spheres in serum-free medium, maintaining the tumorigenicity. Interestingly, a single cancer stem cell generated a cancer sphere that contained various differentiated cells, supporting multi-potency and self-renewal of a cancer stem cell. EpCAM⁺/CD44⁺ cells had greater resistance to anti-cancer drugs than other subpopulation cells. The above in vivo and in vitro results suggest that cancer stem cells, which are enriched in the EpCAM⁺/CD44⁺ subpopulation of gastric cancer cells, provide an ideal model system for cancer stem cell research.