One approach we use is to generate reporter mouse lines, with stem and progenitor cells highlighted by various fluorescent proteins, expressing GFP under the regulator elements of the nestin gene. This showed us the wonderful morphology of adult neural stem cells (green) with the cell body located in a narrow zone under a layer of granule neurons. The neurons extend long processes producing an elaborated arbor of tiny leaf-like processes.
Research
There are several areas of research in the Enikolopov Lab.
Neuronal Stem Cells. Our main focus is on stem cells in the adult organism and on signals controlling their maintenance, division and fate. Most of our effort is directed at stem cells of the adult brain and the signaling landscape of the neural stem cell niche. We proposed a new model for the quiescence, maintenance, and division of the adult hippocampal stem cells. Our results indicate that an adult neural stem cell may remain quiescent for their entire postnatal life, but, when activated, rapidly divides several times in quick succession to bud off daughter cells that eventually yield neurons, while the remaining stem cell differentiates into a mature astrocyte, thus leaving the stem cell pool. Hence, in contrast to the conventional model of recurring stem cell quiescence, an adult hippocampal stem cell can be described as a “single-use” or a “disposable” unit – used in adulthood only once and then abandoned in its stem cell capacity. We also found that astrocytic differentiation of hippocampal stem cells is tightly coupled to their division, that vast majority of dividing stem cells of the hippocampus convert into astrocytes, and, conversely, that new astrocytes of the dentate gyrus derive from these stem cells. We found that continuous loss of stem cells via their division-coupled astrocytic differentiation underlies age-dependent diminished production of new neurons and may contribute to age-related cognitive impairment. We now work to determine whether our model of differentiation-driven stem cell attrition may be relevant to other types of normal and tumor-initiating stem cells. More recently, we started studying the role of neural stem cells and new neurons in behavior, focusing on an animal model of social conflict.
Non-neuronal Stem Cells. We are also interested in stem cells in non-neural tissues, with a particular focus on those tissues and organs that are involved in complex physiological circuits and major physiological and behavioral responses of the organism. We also study how diffusible signaling molecules regulate stem cell maintenance, differentiation, and interactions with their local environment. The current cycle of stem cell studies grows from our interest and research on the biological functions of nitric oxide and redox signaling, a theme that our group continues studying. Our particular interest is in the novel function of NO that we uncovered: the role it plays in the development and function of cilia in multiciliated cells of the ciliated epithelium. Our recent results suggest that certain inborn and acquired human ciliopathies and related disorders may also be associated with decreased availability of NO and may benefit from NO-based therapies.
Genetic Tools for Cell Signaling. We also work to generate new genetic tools for tracking multiple signaling events in a cell or a tissue. Overall, besides the main goal of elucidating the molecular logic of the stem cell control, we consider our studies as an entry point for designing therapeutic intervention to ameliorate the effects of aging or disease.
