Harvard Stem Cell Institute Research Newsletter
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This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month.
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Spotlight
In an article paper published in Nature Neuroscience,
HSCI Principal Faculty Member, Kevin Eggan and Tom Maniatis, a professor in Harvard's Faculty of Arts and Sciences, report that a factor
produced by a form of glial cells causes the damage in motor neurons associated with ALS.
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Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model
Here we report an in vitro
model system for studying the molecular and cellular mechanisms that
underlie the neurodegenerative disease amyotrophic lateral sclerosis
(ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or
mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro
differentiation. These motor neurons could be maintained in long-term
coculture either with additional cells that arose during
differentiation or with primary glial cells. Motor neurons carrying
either the nonpathological human SOD1 transgene or the mutant SOD1G93A allele
showed neurodegenerative properties when cocultured with SOD1G93A glial cells. Thus,
our studies demonstrate that glial cells carrying a human SOD1G93A
mutation have a direct, non-cell autonomous effect on motor neuron
survival. More generally, our results show that ESC-based models of disease provide a powerful tool
for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could
provide cell-based assays for the identification of new ALS drugs.
Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T,
Eggan K
. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model.
Nat Neurosci
. 2007 May;10(5):608-614. Epub 2007 Apr 15.
Read Abstract
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Review and Commentary Articles
- Daley GQ. Gametes from embryonic stem cells: a cup half empty or half full? Science. 2007 Apr 20;316(5823):409-10. Read Abstract.
- Eggan K. Dolly's legacy: human nuclear transplantation and better medicines for our children. Cloning Stem Cells. 2007 Spring;9(1):21-5. Read Abstract.
- Sosnovik DE, Nahrendorf M, Weissleder R. Molecular magnetic resonance imaging in cardiovascular medicine. Circulation. 2007 Apr 17;115(15):2076-86. Read Abstract.
- Schier AF. The maternal-zygotic transition: death and birth of RNAs. Science. 2007 Apr 20;316(5823):406-7. Read Abstract.
- Yu F, Hill RS, Schaffner SF, Sabeti PC, Wang ET, Mignault AA, Ferland RJ, Moyzis RK, Walsh CA, Reich D. Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens". Science. 2007 Apr 20;316(5823):370. Read Abstract.
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| Scientific Papers |
Blood Disease
- Raffel GD, Mercher T, Shigematsu H, Williams IR, Cullen DE, Akashi K, Bernard OA, Gilliland DG. Ott1(Rbm15) has pleiotropic roles in hematopoietic development. Proc Natl Acad Sci USA. 2007 Apr 3;104(14):6001-6. Epub 2007 Mar 21. Read Abstract.
- Gu TL, Mercher T, Tyner JW, Goss VL, Walters DK, Cornejo MG, Reeves C, Popova L, Lee K, Heinrich MC, Rush J, Daibata M, Miyoshi I, Gilliland DG, Druker BJ, Polakiewicz RD. A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia. Blood. 2007 Apr 13; Read Abstract.
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Cardiovascular Disease
- Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR. Postnatal isl1(+) cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2007 Apr 19;446(7138):934. Read Abstract.
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Development
- Trede NS, Medenbach J, Damianov A, Hung LH, Weber GJ, Paw BH, Zhou Y, Hersey C, Zapata A, Keefe M, Barut BA, Stuart AB, Katz T, Amemiya CT, Zon LI, Bindereif A. Network of coregulated spliceosome components revealed by zebrafish mutant in recycling factor p110. Proc Natl Acad Sci USA. 2007 Apr 17;104(16):6608-13. Epub 2007 Apr 6. Read Abstract.
- Vokes SA, Ji H, McCuine S, Tenzen T, Giles S, Zhong S, Longabaugh WJ, Davidson EH, Wong WH, McMahon AP. Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning. Development. 2007 Apr 18; Read Abstract.
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Imaging
- Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, Pande AN, Kohler RH, Shi GP, Libby P, Weissleder R. Optical Visualization of Cathepsin K Activity in Atherosclerosis With a Novel, Protease-Activatable Fluorescence Sensor. Circulation. 2007 Apr 9; Read Abstract.
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Immunology
- Holler PD, Yamagata T, Jiang W, Feuerer M, Benoist C, Mathis D. The same genomic region conditions clonal deletion and clonal deviation to the CD8{alpha}{alpha} and regulatory T cell lineages in NOD versus C57BL/6 mice. Proc Natl Acad Sci USA. 2007 Apr 24;104(17):7187-92. Epub 2007 Apr 16. Read Abstract.
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Nervous System Diseases
- Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 2007 May;10(5):608-614. Epub 2007 Apr 15. Read Abstract.
- Friocourt G, Liu JS, Antypa M, Rakic S, Walsh CA, Parnavelas JG. Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J Neurosci. 2007 Apr 4;27(14):3875-83. Read Abstract.
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Skeletal and Muscle Systems
- Legare F, Pfeffer CP, Olsen BR. The role of backscattering in SHG tissue imaging. Biophys J. 2007 Apr 20; Read Abstract.
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 The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions. Visit our website at www.hsci.harvard.eduIf there is anything that you would like to see added to this email alert, please email maureen_lyons@harvard.edu. |
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