The Control of Proliferation, Migration, and Differentiation of Human Pluripotent Stem Cells-Derived Neural Progenitor Cells by MicroRNAs
Neurodegenerative diseases such as Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease, as well as stroke and spinal cord injuries, pose a serious challenge to our society. All are characterized by neuronal cell loss in specific regions of the brain or spinal cord. It is conceivable that the functions of these regions could be restored by replacing damaged nerve cells through transplantation of stem cells or stem cell–derived progenitor cells. Such cells could differentiate into the desired cell types and then integrate into functional neuronal circuits. Therefore, human embryonic stem cells (hESCs) and induced pluoripotent stem (iPS) cells offer an exciting new approach for treating brain diseases and injuries. However, before clinical applications become a reality, much more needs to be learned about the cellular behaviors of neural progenitor cells (hNPCs) derived from human pluripotent stem cells (hPSCs). For instance, transplanted stem cells or stem cell–derived hNPCs must be prevented from turning into tumors and they must migrate effectively to injured brain regions and incorporate into the damaged neuronal circuitry. Thus, understanding the basic molecular mechanisms that govern the proliferation, migration, and differentiation of hPSC-derived hNPCs is critically important. The studies proposed here will further our understanding of how microRNAs—a recently identified class of small regulatory RNA molecules—control the cellular behaviors of hPSC-derived hNPCs. These studies will provide important mechanistic insights into the basic molecular pathways relevant to human stem cell biology. Since miRNAs are excellent tools for manipulating cellular behaviors and may become feasible targets for therapeutic approaches, the proposed studies will likely contribute to the development of effective stem cell–based therapies for neurodegenerative diseases and brain and spinal cord injuries.
California is the most populous state in the U.S., and many Californians suffer from neurodegenerative diseases and brain and spinal cord injuries. Unfortunately, these insidious conditions remain incurable, and will become more common as the number of people of advanced age increases. Stem cell–based therapies are a promising new approach for these problems; however, much more need to be done to understand the basic biology of human embryonic and induced pluoripotent stem cells. We propose to investigate the roles of a class of small RNA molecules called microRNAs in controlling the proliferation, migration, and differentiation of human neural progenitor cells derived from human stem cells. These studies will help develop feasible therapeutic approaches that will eventually be used to treat patients in California and around the world.