MicroRNA Expression and Control of Stem Cell Pluripotency, Differentiation and Cellular Processes

MicroRNAs (miRNAs) are a class of short non-coding RNAs that bind to the 3' untranslated region of mRNAs and downregulate their translation to protein. MiRNAs play critical roles in many different cellular processes including metabolism, apoptosis, differentiation, and development. Researchers at JHU have investigated the role of miRNAs in the control of stem cell biology and differentiation. Through this work they discovered 33 novel miRNAs expressed by both bone marrow or mobilized peripheral blood stem cell harvests of human hematopoietic stem-progenitor cells (HSPC). The miRNA expression data was compared to mRNA expression from human HSPC using a novel miRNA: mRNA interaction database called the Transcriptome Interaction Database (TID), which is able to generate miRNA-mRNA target predictions. The in silico predictions pointed to miRNA control of hematopoietic differentiation through translational control of mRNAs critical to the process of hematopoiesis. From these predictions, the scientists formulated a model where genes specifying hematopoietic differentiation are expressed by HSPCs, but are held in check by miRNAs until differentiation occurs. The TID predictions were validated by demonstrating that mRNA translation is decreased by miRNAs Description (Set) Proposed Use (Set) The study of stem cells is a young scientific field that holds great promise for the treatment of disease and injury. The invention of Georgantas and colleagues may be used for the ex vivo expansion of undifferentiated stem cells through the use of miRNA to stall cellular differentiation in culture. The hematopoietic miRNAs discovered will also be useful in developing treatments for leukemia. The invention can be used as a research tool to help better understand stem cell pluripotency and the mechanisms that induce differentiation. In addition, the invention will aid in the discovery of specific mRNA and protein targets affected by miRNAs and ultimately, will identify novel proteins with roles in stem cell characteristics and biology. This work will also help to develop agents to profile and identify stem cells based on their miRNA expression, or agents to alter stem cell differentiation or function by expression of specific miRNAs.

Inventor(s): Georgantas, Robert

Type of Offer: Licensing

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