McEwen Monthly

September 2013 | mcewencentre.com

Novel Role for GATA-3 in Regulating Stem Cell Self-Renewal

Although the transcription factor GATA-3 is known to regulate T cell development and function, its role in hematopoiesis has remained uncertain. A recent study published in Nature Immunology by McEwen Centre Researcher Dr. Norman Iscove provides new evidence that GATA-3 plays a role in regulating the function of certain hematopoetic stem cell populations.

Hematopoietic stem cells are categorized into two distinct classes based on their biology and phenotype. Long-term multi-potent hematopoietic stem cells (LT-HSCs) can sustain myeloid, erythroid and lymphoid populations due to their continued ability to self-renew. Intermediate-term HSCs (IT-HSCs) can only sustain myeloid and erythroid populations for about 12 weeks before cell numbers begin to diminish.

Dr. Iscove and his team were able to demonstrate that GATA-3 is present in LT-HSCs and not IT-HSCs, and that it remains inactive when cells are in a quiescent state. Interestingly, when LT-HSCs are signalled to proliferate, GATA-3 is activated—a process that is associated with a reduced capacity of stem cells to sustain hematopoietic populations long-term. By deleting GATA-3, the researchers were able to enhance the ability of LT-HSCs to self-renew without affecting proliferation.

These findings implicate GATA-3 as a key controller of HSC self-renewal and may have important implications for research and therapeutic applications that require the expansion of HSCs.

GATA-3 regulates the self-renewal of long-term hematopoietic stem cells. Frelin C, Herrington R, Janmohamed S, Barbara M, Tran G, Paige CJ, Benveniste P, Zúñiga-Pflücker JC, Souabni A, Busslinger M, Iscove NN. Nature Immunology. August 25 2012. [Pubmed abstract]

This work was funded by grants from the McEwen Centre for Regenerative Medicine, the Terry Fox Foundation, the Canadian Cancer Society Research Institute, the Canadian Institutes of Health Research, the Princess Margaret Cancer Foundation, The Campbell Family Institute for Cancer Research, the Stem Cell Network and the Ontario Ministry of Health and Long-Term Care.


Miniature Brain-like Structures Grown in Lab

Research on brain development has been limited by a lack of experimental models which accurately recapitulate the complexities of the human brain. A recent advancement led by Dr. Juergen Knoblich, at the Institute of Molecular Biotechnology of the Austrian Academy of Science, may have eliminated this roadblock by establishing a novel three-dimensional culture system capable of producing distinct, though interdependent, brain tissues.

This novel culture system will provide stem cell researchers with unprecedented opportunities to model brain disease and will open new lines of research in regenerative medicine. To learn more about this exciting advancement, click here.


McEwen Researcher Featured in Stem Cell Rounds

The first Stem Cell Rounds of the season was held on September 11th, and featured a talk by McEwen Centre Researcher Dr. Norman Iscove titled “Probing stem cell biology cell by cell: where it matters, where it’s just stamp collecting”. The seminar provided new insight on the importance of linking data derived from single cell studies such as mRNA or protein expression to cell function. You can watch a podcast of the event by clicking here.


Canada-Japan Joint Program to Fund Stem Cell Research

McEwen Centre Researchers Drs. Andras Nagy and John Dick have been awarded funding as part of a new initiative that aims to strengthen research collaborations between Japan and Canada. This joint program, launched by the Canadian Institutes of Health Research and the Japan Science and Technology Agency, is designed to position Canada and Japan as leaders in the field of epigenetics and health research. As part of this initiative, Dr. Dick will work with Dr. Hiromitsu Nakauchi (University of Tokyo) to improve methods for engineering stem cells while Dr. Nagy will collaborate with Dr. Yasuhiro Yamada (Kyoto University) to study cellular reprogramming.


2013 Till & McCulloch Meetings

This year's Till & McCulloch meetings, which aim to bring together researchers, clinicians and bioengineers from all areas of stem cell research, will be held in Banff, Alberta on October 23-25, 2013. Speakers at the conference will include Drs. Gordon Keller, Andras Nagy and Freda Miller. For detailed conference information, click here.


Recent Publications

Regenerative therapies for central nervous system diseases: a biomaterials approach.Tam RY, Fuehrmann T, Mitrousis N, Shoichet MS. Neuropsychopharmacology. 2013 Sep 4. [Abstract]

Role of miR-145 in cardiac myofibroblast differentiation. Wang YS, Li SH, Guo J, Mihic A, Wu J, Sun L, Davis K, Weisel RD, Li RK. J Mol Cell Cardiol. 2013 Aug 31. [Abstract]

Modulation of bone marrow mesenchymal stem cell secretome by ECM-like hydrogels. Silva NA, Moreira J, Ribeiro-Samy S, Gomes ED, Tam RY, Shoichet MS, Reis RL, Sousa N, Salgado AJ. Biochimie. 2013 Aug 30. [Abstract]

Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model. Chamankhah M, Eftekharpour E, Karimi-Abdolrezaee S, Boutros PC, San-Marina S, Fehlings MG. BMC Genomics. 2013 Aug 28.[Abstract]

GATA-3 regulates the self-renewal of long-term hematopoietic stem cells. Frelin C, Herrington R, Janmohamed S, Barbara M, Tran G, Paige CJ, Benveniste P, Zuñiga-Pflücker JC, Souabni A, Busslinger M, Iscove NN. Nat Immunol. 2013 Aug 25. [Abstract]

Secondary cell reprogramming systems: as years go by. Nagy A. Curr Opin Genet Dev. 2013 Aug 19. [Abstract]

The responses of neural stem cells to the level of GSK-3 depend on the tissue of origin. Holowacz T, Alexson TO, Coles BL, Doble BW, Kelly KF, Woodgett JR, van der Kooy D. Biol Open. 2013 Aug 15. [Abstract]

Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. Taniguchi K, Xia L, Goldberg HJ, Lee KW, Shah A, Stavar L, A Y Masson E, Momen A, Shikatani EA, John R, Husain M, Fantus IG. Diabetes. 2013 Aug 13. [Abstract]

Differential transformation capacity of neuro-glial progenitors during development. Muñoz DM, Singh S, Tung T, Agnihotri S, Nagy A, Guha A, Zadeh G, Hawkins C. Proc Natl Acad Sci USA. 2013 Aug 27. [Abstract]

Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, Figueiredo JL, Gorbatov R, Sukhova GK, Gerhardt LM, Smyth D, Zavitz CC, Shikatani EA, Parsons M, van Rooijen N, Lin HY, Husain M, Libby P, Nahrendorf M, Weissleder R, Swirski FK. Nat Med. 2013 Sep. [Abstract]

Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke. Wang Y, Cooke MJ, Sachewsky N, Morshead CM, Shoichet MS. J Control Release. 2013 Aug 9. [Abstract]

Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery. Chan DP, Deleavey GF, Owen SC, Damha MJ, Shoichet MS. Biomaterials. 2013 Nov. [Abstract]

Bone marrow-derived progenitor cells in end-stage lung disease patients. Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK. BMC Pulm Med. 2013 Aug 3. [Abstract]

Mesenchymal stromal cells augment CD4+ and CD8+ T cell proliferation through a CCL2 pathway. Zhou Y, Day A, Haykal S, Keating A, Waddell TK. Cytotherapy. 2013 Oct. [Abstract]