Year 2

Stem cells are the building blocks during development of organisms as varied as plants and humans. In addition, adult or “tissue” stem cells provide for the maintenance and regeneration of tissues, such as blood and skin throughout the lifetime of an individual. The ability of stem cells to contribute to these processes depends on their unique ability to divide and generate both new stem cells (self-renewal) as well as specialized cell types (differentiation).

In some tissues, cells that have already begun to specialize can revert or “de-differentiate” and assume stem cell properties, including the ability to self-renew. De-differentiation of specialized cells could provide a “reservoir” of cells that could act to replace stem cells lost due to wounding or aging. This proposal seeks to uncover the mechanisms that are utilized to regulate the process of de-differentiation and to compare these to the mechanisms that endow stem cells with the ability to self-renew. Understanding the mechanisms by which partially differentiated cells can reacquire self-renewal potential and how these programs are utilized during the normal course of tissue maintenance and repair could provide powerful strategies for regenerative medicine by stimulating inherent self-repair programs normally present within tissues and organs.

In the most recent funding period, we have focused primarily on understanding the role of a candidate protein, human Igf-II mRNA binding protein (hIMP1), that likely plays a role in enhancing the de-differentiation of committed cells back to a pluripotent stem cell state in mammalian systems. Published data indicate that hIMP1 is highly expressed in most tissue during development and that IMP1 is reportedly down-regulated in all tissues, except gonads, after birth. In contrast, our preliminary data suggest that IMP1 is highly expressed in human pluripotent stem cells as well as in some adult tissue stem and progenitor cells. Our focus in the coming year will be to address the role of hIMP1 in regulating the proliferation and differentiation of human stem cells.