TIGP (BIO)—Unraveling the Dynamics of Genome Alteration in Embryonic Neural Progenitor Cells

Abstract

Embryonic neural progenitor cells undergo hundreds of cell divisions to generate the 80 billion neurons in a human brain. In neural progenitor cells, replication stress can lead to recurrent DNA break occurring to gene regulating neuronal functions. Joining of two RDC breaks may introduce somatic genomic diversity. On the other hand, unbalanced genomic mosaicism in neural progenitor cells may lead to brain cancer and neuropsychiatric disorders. This seminar will address two fundamental processes that influence the dosage of DNA alteration in the brain cell populations. Firstly, we will examine the intricate interplay between DNA replication and transcription, elucidating how their linear interaction influences genome fragility in neural stem and progenitor cells. Secondly, we will explore the phenomenon of clonal evolution, wherein competition among neural progenitor cells during brain development shapes the burden of genome alteration. This seminar will showcase the integration of cutting-edge methodologies, including multi-omics analysis, mathematical modeling, and genomics, to tackle these challenging biological questions. By dissecting the molecular mechanisms underlying genome alteration in embryonic neural progenitor cells, we aim to unravel fundamental insights into brain development and pathology, with implications for understanding and potentially mitigating neurological disorders.

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