bioRxiv Subject Collection: Neuroscience's Journal
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Monday, January 22nd, 2024
| Time |
Event |
| 11:18a |
Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids
Disruptions in the tightly regulated process of human brain development have been linked to increased risk for brain and mental illnesses. While the genetic contribution to these diseases is well established, important environmental factors have been less studied at molecular and cellular levels. In this study, we used single-cell and cell-type-specific techniques to investigate the effect of glucocorticoid (GC) exposure, a mediator of antenatal environmental risk, on gene regulation and lineage specification in unguided human neural organoids. We characterized the transcriptional response to chronic GC exposure during neural differentiation and studied the underlying gene regulatory networks by integrating single-cell transcriptomics- with chromatin accessibility data. We found lasting cell type-specific changes that included autism risk genes and several transcription factors associated with neurodevelopment. Chronic GCs influenced lineage specification primarily by priming the inhibitory neuron lineage through key transcription factors like PBX3. We provide evidence for convergence of genetic and environmental risk factors through a common mechanism of altering lineage specification. | | 11:18a |
Topographic, cognitive, and neurobiological profiling of the interdependent structural and functional connectome in the human brain
The structural connectome (SC) is tightly coupled to the functional connectome (FC) in the human brain. Most previous related studies have modeled and analyzed SC or FC as isolated brain networks. However, challenges remain in modeling the interdependent structural-functional connectome and elucidating its cognitive implications and molecular underpinnings. Here, we present a multilayer connectome model composed of SC and FC components and further characterize their interacting topological properties. We found that the interdependent connectome is topographically heterogeneous, with the transmodal cortex exhibiting greater modular variability across layers. This spatial topography reflects cortical hierarchy and evolution and shows high test-retest reliability, reproducibility, and heritability. The interdependent connectome contributes to high-order cognitive processes and is associated with multiple neurotransmitter systems and transcriptional signatures of synaptic transmission. Our results provide insights into the nontrivial interdependencies of SC and FC, highlighting their cognitive significance and the molecular mechanisms underlying the connectome of connectomes. |
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