LSI Seminar Series: Time to wake up — Regulation of neural stem cell quiescence
Time to wake up: Regulation of neural stem cell quiescence
Quiescence is an actively maintained state of reversible cell cycle arrest: cells stop proliferating and remain stalled in either the G0 or G2 phase of the cell cycle. Both developing and adult tissues maintain pools of quiescent stem cells. Cell cycle re-entry (reactivation) of quiescent stem cells occurs during growth and in response to injury or disease, to generate or replace differentiated cells. During Drosophila development, neural stem cells become quiescent in late embryogenesis and reactivate in early larval development, giving rise to neurons and glia that contribute to the adult nervous system. Reactivation of quiescent neural stem cells (qNSCs) is a coordinated process that generates new neurons and glia to maintain homeostasis or enable repair post-injury. We discovered that NSC reactivation follows a hierarchical sequence, whereby anterior qNSCs in the brain lobes control the timely reactivation of more posterior qNSCs in the ventral nerve cord. To achieve this, qNSCs transiently express neuronal genes and contact neurons to relay reactivation. This transient neuronal state is unique to qNSCs, as neuronal genes are turned off once stem cells resume proliferation. Our results reveal long-range communication between qNSCs that coordinates reactivation across the entire CNS, enabled by a transient, remarkably plastic, neuronal-like stem cell state that allows direct interaction with axons.
Speaker
Andrea H. Brand received her B.A. from Oxford University and her Ph.D. from the MRC Laboratory of Molecular Biology, University of Cambridge, working with Kim Nasmyth. After postdoctoral fellowships with Mark Ptashne at the Department of Biochemistry and Molecular Biology, Harvard University, and with Norbert Perrimon at the Department of Genetics, Harvard Medical School, she returned to the UK to become a Wellcome Trust Senior Fellow at the Gurdon Institute, University of Cambridge. She became Director of Research in Developmental Neurobiology in 2003 and Senior Group Leader in 2005. She was appointed Herchel Smith Professor in Molecular Biology in 2007 and Royal Society Darwin Trust Research Professor in 2015. She was Head of Wellcome Trust Laboratories at the Gurdon Institute from 2015-2022.
Andrea Brand was awarded the Royal Society Rosalind Franklin Award in 2006, the William Bate Hardy Prize, jointly with Professor Robin Irvine, in 2004, the Hooke Medal of the British Society of Cell Biology in 2002 and a Special Award of Excellence at the Wellcome Biomedical Imaging Awards, 2001. She was elected a Fellow of the Royal Society in 2010, Fellow of the Academy of Medical Sciences in 2003, member of the European Molecular Biology Organization in 2000 and was previously a Leukemia Society Special Fellow and a Helen Hay Whitney Fellow.
The Brand lab studies the genetic networks that regulate the transition from a multipotent neural stem cell to a specialized neuronal or glial cell type, and those that direct cellular regeneration. With sufficient knowledge of these networks, it should be possible to manipulate stem cells to proliferate, to remain quiescent, or to differentiate into specialised, predefined, cell types at will.