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Davis et al. (p 62) report that disruption of key homeostatic morphogen signaling gradients in the intestine results in the expansion of a population of proliferating progenitor cells outside of the crypt base stem cell niche. These cells do not express the intestinal stem cell marker Lgr5, yet form ectopic crypts on the villus, acquire somatic mutations and initiate tumorigenesis. The image shows immunohistochemical staining for an Lgr5-EGFP reporter gene in the small intestine of a mouse expressing a transgene encoding the bone morphogenetic protein antagonist Grem1 in intestinal epithelial cells. Lgr5-EGFP positive cells (brown) are found at the base of the intestinal crypts, but not in ectopic crypt foci on the villus. Original image by Hayley Davis.
A refocused scope will infuse new technology into the regular research section of Nature Medicine and strengthen the synergy between regular research articles and Technical Reports.
The growth factor thrombopoietin (TPO) drives platelet biogenesis by inducing megakaryocyte production. A new study in mice identifies a feedback mechanism by which clearance of aged, desialylated platelets stimulates TPO synthesis by hepatocytes.
CD4+ helper T cells are immune cells that can specifically target cancer cells, but the antigens they recognize on tumor cells are mostly unknown. A new study shows that CD4+ T cells recognize peptides encoded by mutated genes in human melanoma, opening the way for new approaches to cancer immunotherapy.
Endogenous expression of tailored nanoparticles in cells followed by application of low-frequency radio waves or a magnetic field can be used to noninvasively modulate gene expression. This approach successfully induces insulin transgene expression in diabetic mice.
Notch signaling regulates developmental processes. A new study in mice shows that Notch signaling regulates the maintenance and survival of memory CD4+ T lymphocytes through a mechanism involving glucose uptake, and it suggests that Notch signaling can be modulated to treat autoimmune conditions.
A rationally designed peptide agonist that targets three key hormone receptors reduces obesity and its complications in a manner superior to other agonists.
Binding of aged, desialylated platelets to the Ashwell-Morell receptor induces hepatic expression of the cytokine thrombopoietin via JAK2-STAT3 signaling, providing a feedback mechanism to control platelet production.
The authors report a mechanistic basis for intestinal polyp formation in patients with hereditary mixed polyposis syndrome that involves the aberrant epithelial expression of morphogens and leads to the formation of ectopic intestinal crypts by progenitor cells outside the stem cell niche, a mechanism that seems to also be involved in human ectopic serrated polyps.
Loss of muscle satellite cells during aging has been thought to contribute to sarcopenia, but experimentally induced depletion of these cells in adult mice does not result in this condition.
Georgiou and colleagues describe a single-cell, emulsion-based approach for the high-throughput determination of the paired antibody variable heavy and light chain (VH-VL) repertoire encoded by the more than 2 × 106 B cells in human peripheral blood samples.
Development and validation of a genetically encoded system in which gene expression is regulated remotely and noninvasively by either low-frequency radio waves or a static magnetic field.