1. Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis
- Author
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Mukhtar, Tanzila, Breda, Jeremie, Adam, Manal A, Boareto, Marcelo, Grobecker, Pascal, Karimaddini, Zahra, Grison, Alice, Eschbach, Katja, Chandrasekhar, Ramakrishnan, Vermeul, Swen, Okoniewski, Michal, Pachkov, Mikhail, Harwell, Corey C, Atanasoski, Suzana, Beisel, Christian, Iber, Dagmar, Nimwegen, Erik, and Taylor, Verdon
- Subjects
Biomedical and Clinical Sciences ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,Regenerative Medicine ,Stem Cell Research - Embryonic - Non-Human ,Genetics ,Neurosciences ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Animals ,Mice ,Cell Differentiation ,Cell Lineage ,Cerebral Cortex ,Embryonic Stem Cells ,Neural Stem Cells ,Neurogenesis ,Neurons ,cortical development ,lineage specification ,networks ,signaling pathways ,transcriptional landscape ,Biological Sciences ,Information and Computing Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders.
- Published
- 2022