Haematopoiesis

Hematopoietic stem cells engraft in mice with absolute efficiency. Benveniste, P. et al. Nature Immunol. 25 May 2003 (DOI: 10.1038/ni940)

Haematopoietic stem cells (HSCs) are unique in that they can self renew, are pluripotent and can differentiate into blood cells of all lineages. Transfer of mouse HSCs to irradiated mice can restore haematopoiesis in the recipient but, until now, this process was thought to be inefficient. Using two independent experimental approaches, Benveniste et al. show, in contrast to previous studies, that when single purified HSCs are injected into recipient mice, nearly all of these result in successful engraftment. However, only a minority of these cells established grafts that were long lasting, indicating that it is the ability to retain self-renewal capabilities rather than inefficient initial engraftment that reduced the success of previous attempts to engraft mice in this way.

Gene Therapy

Transcription start regions in the human genome are favored targets for MLV integration. Wu, X. et al. Science 300, 1749–1751 (2003)

Retroviruses, including mouse leukaemia virus (MLV), are efficient gene-delivery vehicles that have been used in many gene-therapy trials. It was believed that retroviruses integrated randomly into the genome, but recent developments indicate that this might not be so. Here, a high-throughput method was used to clone the genomic regions that are adjacent to the integration sites. 903 MLV and 379 HIV-1 pro-viral integrations in the human genome were mapped in this study. MLV preferentially integrated near the transcription-start site of active genes, and HIV-1 showed a preference for transcribed regions. This work provides an insight into the mechanisms of pro-virus integration and shows that these differ between retroviruses, which could have important implications for gene-therapy trials.

Lymphocyte Migration

Microangiectasias: structural regulators of lymphocyte transmigration. Secomb, T. W. et al. Proc. Natl Acad. Sci. USA 100, 7231–7234 (2003)

Lymphocyte migration is thought to occur as a result of a multi-step adhesion cascade. According to this model, localized expression of adhesion molecules by endothelial cells allows lymphocytes to overcome the flow shear forces. Shear stresses in normal vessels are ∼20 dyn/cm2, but lymphocyte adhesion usually occurs at wall shear stresses of ∼1dyn/cm2. Furthermore, blood flow during inflammation is likely to increase the shear stresses rather than decrease them. Now, Secomb and colleagues present data to support the idea that lymphocyte migration actually occurs in specialized vascular regions. They detected focal structural dilations — microangiectasias — in the vessels, in which shear forces are reduced sufficiently to allow lymphocyte–endothelial cell interactions to occur.