Harvard Stem Cell Institute Monthly Update
Highlights from Selected Projects
October, 2008
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| Kidney Development
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| The basic functional units of the kidney, the nephrons, develop during kidney formation. However, it has been difficult to determine the cells from which the nephrons develop and how the nephron lineages are specified. Recently, HSCI faculty member Andy MacMahon and colleagues identified a group of cells in the developing kidney, distinguishable by their expression of the Six2 gene, which can differentiate into all of the nephron cell types and represent a nephron progenitor cell. This advance has exciting potential implications for the large number of people with kidney disease given the current dearth of effective treatments for kidney disease and the difficulties associated with kidney transplants. Identifying this nephron progenitor population opens the door for cell-based therapies for kidney disease such as cell transplants and cell replacement therapies.
Kobayashi, A., Valerius, M.T., Mugford, J.W., Carroll, T.J., Self, M., Oliver, G., McMahon, A.P. (2008). Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3, 169-81.
| | Stem Cell Niches |
| The behavior of stem cells is greatly influenced by their microenvironment, or niche. The niche may influence their rate of cell division, differentiation, and migration away from the niche to other parts of the body. One of the best-studied systems for studying the interaction between stem cells and their niche is the hematopoietic, or blood-forming, stem cells (HSCs) and their niche in the bone marrow. The HSC niche contains a variety of cell types and the way in which these different cell types contribute to fostering the HSC niche remains unclear. Recently, an exciting finding by HSCI Scientific Co-director and faculty member, David Scadden, and colleagues discovered that a tumor suppressor gene, Nf2, and its protein product merlin, is required in the HSC niche to keep the cells properly localized and maintain the number of cells in the HSC pool. This gene appears to exert these effects by maintaining the architecture of the HSC niche, potentially by enabling other factors to act directly on HSCs. This finding is significant because it brings us one step closer toward understanding how HSCs are regulated within their niche.
Larsson, J., Ohishi, M., Garrison, B., Aspling, M., Janzen, V., Adams, G.B., Curto, M., McClatchey, A.I., Schipani, E., Scadden, D.T. (2008). Nf2/merlin regulates hematopoietic stem cell behavior by altering microenvironmental architecture.
Cell Stem Cell 3, 221-7
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| | iPS Cells |
| One stem cell breakthrough that has been in the news quite a bit this past year is nuclear reprogramming and the creation of induced pluripotent stem (iPS) cells. iPS cells are created when researchers take a somatic cell, such as a skin cell, in the laboratory and reprogram it by adding factors that induce it to have features resembling an embryonic stem cell. One of the potential benefits of iPS cells could be to produce disease-specific cell lines from a patient with a particular disease. These cells could represent a plentiful cell source to be used in high-throughput screens to identify potential therapeutics, or to study disease mechanisms. However, one of the limiting factors for clinical applications is that iPS cells are currently created using viruses to introduce the necessary factors that insert into the genomic DNA and may be potentially mutagenic. A key advance by HSCI faculty member Konrad Hochedlinger and colleagues showed that they were able to create mouse iPS cells using a method in which the adenovirus used to introduce the necessary factors does not integrate into the genome and would therefore not be cancer causing. These "adeno-iPS" cells thus address one of the challenges facing reprogramming, potentially bringing the technology one step closer to the clinic.
Stadtfeld, M., Nagaya, M., Utikal, J., Weir, G., Hochedlinger, K. (2008)
Induced Pluripotent Stem Cells Generated Without Viral Integration.
Science. 2008 Sep 25. [Epub ahead of print] | For more about the Harvard Stem Cell Institute, visit
www.hsci.harvard.edu/ |
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