The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: July 5, 2013

A few weeks ago I reviewed a paper that demonstrated that pluripotent stem cells could be induced by repressing muscleblind-like RNA binding (MBNL) proteins in differentiated cells. Continuing in this vein, new research published in Nature Cell Biology from the lab of Dr. Connie Eaves at the BC Cancer Agency identifies a pathway crucial for the maintenance of the self-renewal properties of hematopoietic stem cells (HSCs). Using array analysis and quantitative polymerase chain reaction, the authors found that the Lin28b gene is expressed much more highly in mouse fetal liver HSCs than in adult bone marrow HSCs, which have greatly reduced self-renewal capabilities compared to fetal liver HSCs. Adult bone marrow HSCs transfected with the Lin28 gene and subsequently transplanted in to mice of at least 10 weeks of age have increased self-renewal capabilities and also show decreased levels of let-7 microRNA, the production of which is inhibited by Lin28b. Additionally, flow cytometry experiments demonstrated that Hmga2, a protein that is known to be inhibited by let-7, was increased in adult bone marrow HSCs following Lin28 transfection. Directly increasing Hmga2 levels in adult bone marrow HSCs increased the self-renewing capabilities of these cells, whereas fetal liver cells lacking Hmga2 have greatly reduced self-renewing capability. Overall, this study demonstrates that the self-renewing capability of mouse hematopoietic stem cells is regulated by the Lin28 – let-7 – Hmga2 axis, which is down-regulated within a few weeks following birth. Thus, this pathway offers a potential target for the development of tissue-specific self-replicating cells, which promise to be very important for the treatment of a variety of diseases.

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