Meng Li
Stem cells, neuronal development, and the cellular basis of neuropsychiatric diseases
Meng Li, Cardiff University
11:50 -12:50 BST, Tuesday 25th April 2023
The primary research interest of Meng Li's laboratory is to uncover the molecular mechanisms underlying neuronal subtype specification of pluripotent stem cells and during mammalian development.
Over the years, the lab has contributed to the advance in understanding pluripotent stem cell (PSC) neural fate conversion and dopaminergic fate specification of PSCs and during normal mammalian development. These studies led to the establishment of valuable 'tool boxes' for lineage-specific marking of defined stem/progenitors and mature dopamine neurons, and efficient novel methods for directed neuronal differentiation.
Recently, their interest has extended into GABAergic cortical interneurons, a complex group of cells which dysfunction has been implicated in neuropsychiatric diseases and epilepsy.
Stem cells, neuronal development, and the cellular basis of neuropsychiatric diseases
Neurodevelopmental disorders (NDD) such as autism are a group of mental disorders that affect the development of the nervous system and present an immense personal and societal burden. Current treatments are at best palliative, often ineffective and associated with a variety of debilitating side-effects. Despite major breakthroughs in identifying disease risk genes, our knowledge on the stage of development, cell type, neural circuit and brain region affected by the genetic changes, remains limited. This significant unmet need has impeded the design of rational and effective therapies. In vitro generation of human neurons from pluripotent stem cells (PSCs) carrying disease risk genes and genomic loci provide unprecedented opportunities to study the effects of associated disease mutations on neural development and neuronal function. In this talk, I will discuss current knowledge on neural circuits affected by NDD and our efforts in generating disease relevant neuronal subtypes from human PSCs. I will then zoom in to a current study where we invested neurodevelopmental process of a human PSCs model of 15q11.2 copy number variance (CNV), deletions and duplications of this CNV containing the CYFIP1 gene have been associated with autism and schizophrenia. We identified distorted kinetics in cortical neurogenesis during differentiation of patient-derived iPSCs carrying 15q11.2 deletion and genetically manipulated hESCs with CYFIP1 gain- and loss-of-function (GoF and LoF). I will discuss the experimental evidence that delineates liver X receptor mediated oxysterol regulation of neurogenesis as a novel pathological mechanism in neural cells carrying 15q11.2CNV.
This plenary is part of the The Guarantors of Brain programme stream, convened by The Guarantors of Brain in its role as special partner for BNA2023. The Guarantors of Brain is a charity that aims to promote teaching, education and research in neurology and related clinical-academic disciplines, funded by the publications of the Journal BRAIN and BRAIN Comms.
Being a Special Partner means that The Guarantors of Brain has high level involvement across all aspects of BNA2023, owns a dedicated stream running throughout the Festival programme, and people associated with The Guarantors of Brain can attend the meeting at reduced registration rates (click here for eligiblity).