Epigenetic Regulation of Stem Cell Differentiation
Recent findings published in Developmental Cell by Dr. Freda Miller and colleagues revealed that epigenetic changes can regulate the behaviour of somatic tissue stem cells. Researchers analyzed the CREB binding protein (CBP) histone acetyltransferase to identify how it regulates neural differentiation and how phosphorylation of CBP acts as an epigenetic switch to promote differentiation.
CBP haploinsufficiency results in a genetic disorder with cognitive dysfunction, known as Rubinstein-Taybi syndrome. Miller's group used normal and cbp+/- mouse models to demonstrate that CBP regulates cortical precursor differentiation, rather than cell survival or proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that the pattern of histone acetylation found at neural promoters is similar to CBP binding in wild-type mice; however, decreased CBP binding and acetylation are observed in cbp+/- mice. The use of a histone deacetylase inhibitor (TSA) not only rescued the decreased acetylation observed in Cbp+/- mice, but also rescued neural differentiation. The group further showed that phosphorylation of CBP by atypical protein kinase C ζ is necessary for histone acetylation and to promote differentiation of neural precursor cells into astrocytes and oligodendrocytes.
These findings demonstrate an important mechanism, which may be applicable to other developing or adult stem cell populations, whereby environmental cues regulate stem cell epigenetic status and directly promote differentiation.
CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain. Wang J, Weaver IC, Gauthier-Fisher A, Wang H, He L, Yeomans J, Wondisford F, Kaplan DR, Miller FD. Dev Cell. 2010 January 19. [Abstract]
McEwen Researcher in the News
Dr. Shaf Keshavjee was recently featured in the Feb 21st, 2010 issue of the Toronto Star for his innovative lung transplant research.
The article described his novel use of the NovaLung, an artificial lung that is used to prolong life until a donor lung can be found, as well as the Toronto XVIVO Lung Perfusion System that allows donor lungs to be assessed and repaired prior to transplant.
Mark Your Calendars!
The ESTOOLS International Scientific Symposium on “Stem Cells in Biology and Disease” will be held May 26-28, 2010 in Lisbon, Portugal. Speakers include the McEwen Centre’s Dr. Andras Nagy and a Keynote Address by noted stem cell researcher Dr. Shin Yamanaka. The deadline for abstract submission is March 22, 2010. For more information, please see: http://www.estools.eu/Lisbon
The Toronto Western Research Institute (TWRI) Research Day will be held on Wednesday, May 12, 2010. All TWRI staff, students and researchers are welcome to attend. The oral and poster abstract submission deadline is March 24, 2010. Please see for more information and to register: http://www.uhnres.utoronto.ca/events/twhrd/
March 17, 2010 - Matthew Bjerknes Department of Medical Biophysics, University of Toronto
Cell Lineage Metastability
Location and Time: Red Seminar Room, 2nd Floor, TDCCBR Building, 160 College Street, 4-5 pm
Recent Publications
What's new in cardiac cell therapy? Kinkaid HY, Huang XP, Li RK, Weisel RD. J Card Surg. 2010 February 9. [Abstract]
Functions of type II pneumocyte-derived vascular endothelial growth factor in alveolar structure, acute inflammation and vascular permeability. Mura M, Binnie M, Han B, Li C, Andrade CF, Shiozaki A, Zhang Y, Ferrara N, Hwang D, Waddell TK, Keshavjee S, Liu M. Am J Pathol. 2010 February 18. [Abstract]
Glucagon-like peptide (GLP)-1(9-36) amide-mediated cytoprotection is blocked by exendin(9-39) yet does not require the known GLP-1 receptor. Ban K, Kim KH, Cho CK, Sauvé M, Diamandis EP, Backx PH, Drucker DJ, Husain M. Endocrinology. 2010 February 19. [Abstract]
Transmembrane potential induced on an internal organelle by a time-varying magnetic field: a model study. Ye H, Cotic M, Kang EE, Fehlings MG, Carlen PL. J Neuroeng Rehabil. 2010 February 20. [Abstract]
Pre-hospital care management of a potential spinal cord injured patient: A systematic review of the literature and evidence based guidelines. Ahn H, Singh J, Nathens A, Macdonald R, Travers A, Tallon JM, Fehlings M, Yee A. J Neurotrauma. 2010 February 22. [Abstract]
Os odontoideum: etiology and surgical management. Arvin B, Fournier-Gosselin MP, Fehlings MG. Neurosurgery. 2010 March. [Abstract]
Isoform-specific p73 knockout mice reveal a novel role for {Delta} Np73 in the DNA damage response pathway. Wilhelm MT, Rufini A, Wetzel MK, Tsuchihara K, Inoue S, Tomasini R, Itie-Youten A, Wakeham A, Arsenian-Henriksson M, Melino G, Kaplan DR, Miller FD, Mak TW. Genes Dev. 2010 March 1. [Abstract]
Constrictive pericarditis after lung transplantation: An under-recognized complication. Karolak W, Cypel M, Chen F, Daniel L, Chaparro C, Keshavjee S. J Heart Lung Transplant. 2010 March 4. [Abstract]
Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgcnull recipients. Notta F, Doulatov S, Dick JE. Blood. 2010 March 5. [Abstract]
Dismal response to high-dose methylprednisolone after failure to respond to standard dose in patients with acute GVHD. Schechter T, Macartney C, Finkelstein Y, Gassas A, Husain M, Doyle J, Dupuis LL. Bone Marrow Transplant. 2010 March 8. [Abstract]
The McEwen Centre for Regenerative Medicine, led by director Dr. Gordon Keller, includes 15 scientists at the University of Toronto and five Toronto hospitals, working to advance the development of more effective treatments for conditions including heart disease, diabetes, respiratory disease and spinal cord injury.
The Centre is located at University Health Network, MaRS Centre, Toronto Medical Discovery Tower, 101 College Street, 8th Floor, Room 701, Toronto, Ontario, Canada M5G 1L7
Email: mcewencentre@uhn.on.ca
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