‘The Molecular Regulation of Stem Cell Quiescence’ Webinar
October 16th, 2013
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Dr. Rando participated in a webinar hosted by the journal ‘Current Opinion in Cell Biology’, and sponsored by Beckman Coulter. A recording is available on demand at the link to the left.
Many adult stem cells reside in the quiescent state, or the G0 state of the cell cycle, for prolonged periods of time. This state, one reversible cell cycle withdrawal, has long been viewed as a dormant state with minimal basal activity. However, increasingly there is evidence that suggests that quiescent cells have specific transcriptional, post-transcriptional and metabolic programs that serve at least two functions. The first is to actively maintain the quiescent state, indicating that this is not simply a state of dormancy but in fact under active regulation. The second is to prime the cells for activation, a process that is characterized by the upregulation of multiple cellular processes necessary for cells to enter the cell cycle and begin the process of differentiation.
Skeletal muscle stem cells, or satellite cells, have proven to be extremely valuable in the study of stem cell quiescence because they persist in the quiescent state for weeks, months, and at least in long-lived mammals, perhaps years. In addition, they can be readily identified in situ, they can be rapidly purified by FACS at very high yield and very high purity, and the states of quiescence, activation and “re-quiescence” (i.e. the process by which a proliferating cell returns to quiescence in the process of stem cell self-renewal) can be modeled and studied in vitro. We have focused our studies of stem cell quiescence on this population, and we have discovered unexpected levels of regulation of quiescence and activation. These include the maintenance of the quiescent state by quiescence-specific miRNAs and by active signaling via the Notch pathway. Recent epigenetic profiling using ChIP-seq analysis has revealed evidence of dynamic regulation of chromatin in quiescent stem cells and intriguing epigenetic changes that occur during chronological stem cell aging. Finally, recent results from our laboratory have revealed an unexpected ability of quiescent stem cells to respond to systemic signals and poise themselves in a “pre-activation” state, which we call the “alert state”, and which suggests that in addition to the traditional cell cycle there is also a “quiescence cycle” that allows stem cells to cycle between the quiescent state and the alert state while remaining in G0. Deciphering the molecular mechanisms regulating the quiescent state of adult stem cells will offer new insights into how tissue regeneration is accomplished and how it is dys regulated in pathological conditions and in ageing.
NIH Transformative Research Award: ‘A New Muscle-Brain Axis Underlying the Cognitive Benefits of Physical Activity’
September 30th, 2013
Dr. Rando and his co-principal investigator, Tony Wyss-Coray, PhD, were awarded one of 10 Transformative Research by the NIH. These awards, open to both individuals and teams of investigators, were created to support research projects that have the potential to create or overturn fundamental paradigms.
“Thomas Rando, MD, PhD, professor of neurology, and Tony Wyss-Coray, PhD, professor of neurology and a senior research career scientist at the Veterans Affairs Palo Alto Health Care System, have received a $4.26 million award to explore the basis for physical activity’s robust positive effect on cognitive function.
Aging is associated with a progressive decline in cognitive ability, the consequences of which can be enormous for individuals and society. Muscle is increasingly understood to be a secretory tissue with effects on bone structure, metabolism and blood vessel formation.
Using innovative experimental models and tools, the Rando and Wyss-Coray teams will test the idea that factors produced in exercised muscle are secreted into the circulation, where they gain access to the brain and induce cognitive benefits. In particular, the researchers will investigate the mechanisms by which the profile of factors secreted by muscle tissue changes during exercise.
Further, they will identify the neural cells whose behavior is modified by those secreted factors and that mediate the effects those factors induce during exercise, as well as afterward. The results of these endeavors may drastically alter current thinking about exercise’s beneficial effects on the brain cells’ function and regeneration, remodeling of neuronal circuitry, and cognition itself.
Rando Cell Reports podcast
July 25th, 2013
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How sleeping muscle stem cells might be awakened to fight aging, with Thomas Rando (9:42) (Cell Reports).
Plus, sample a selection of the hottest new papers from Cell Press (19:30).
Scientists discern signatures of old versus young stem cells
July 2nd, 2013
BY BRUCE GOLDMAN
A chemical code scrawled on histones — the protein husks that coat DNA in every animal or plant cell — determines which genes in that cell are turned on and which are turned off. Now, Stanford University School of Medicine researchers have taken a new step in the deciphering of that histone code.
In a study published June 27 in Cell Reports, a team led by Thomas Rando, MD, PhD, professor of neurology and neurological sciences and chief of the Veterans Affairs Palo Alto Health Care System’s neurology service, has identified characteristic differences in “histone signatures” between stem cells from the muscles of young mice and old mice. The team also distinguished histone-signature differences between quiescent and active stem cells in the muscles of young mice.
Full Article Related Article
Rando Video: Telethon’s Scientific Committee: The Focus on Patient’s Needs
June 22nd, 2013
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Fondazione Telethon invests in research in Italy to find cures for rare genetic diseases. Dr. Rando has been a member of the Telethon Scientific Committee since 2009.
The 30 members of the Telethon Scientific Committee met on June 20-21 to give their final assessment of 160 projects that have passed all previous stages of the 2013 selection process.