Biology subjects

Cheng, Y.-T.

Publications and source records attributed to Cheng, Y.-T..

4 recordsLinked to original sources

bioRxiv2023

Remote neuronal activity drives glioma infiltration via Sema4f

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity dependent infiltrating population present at the leading edge of mouse and human tumors that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified Sema4F as a key regulator of tumorigenesis and activity-dependent infiltration. Furthermore, Sema4F promotes the activity-dependent infiltrating population and propagates bi-directional signaling with neurons by remodeling tumor adjacent synapses towards brain network hyperactivity. Collectively, our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, while revealing new mechanisms of tumor infiltration that are regulated by neuronal activity.

cancer biology↗

bioRxiv2023

Inhibitory input directs astrocyte morphogenesis through glial GABABR

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.

neuroscience↗

bioRxiv2023

Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation

Neuronal activity drives global alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. Here we show that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduces serotonin levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduces expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study reveals that neuronal activity orchestrates transcriptional and epigenomic responses in astrocytes, while illustrating new mechanisms for how astrocytes process neuromodulatory input to gate neurotransmitter release for sensory processing.

neuroscience↗

bioRxiv2021

Mindfulness Training Alters Resting-State EEG Dynamics in Novice Practitioners via Mindful Breathing and Body-scan

Mindfulness-based stress reduction (MBSR) has been proven to improve mental health and quality of life. This study examined how mindfulness training and various types of mindfulness practices altered brain activity. Specifically, the spectral powers of scalp electroencephalography (EEG) of the MBSR group who underwent an 8-week mindfulness training--including mindful breathing and body-scan--were evaluated and compared with those of the waitlist controls. Empirical results indicated that the long-term mindfulness intervention effect significantly elevated the resting-state beta powers and reduced resting-state delta powers in both practices; such changes were not observed in the waitlist control. Compared with mindful breathing, body-scanning resulted in an overall decline in EEG spectral powers at both delta and gamma bands among trained participants. Together with our preliminary data of expert mediators, the aforementioned spectral changes were salient after intervention, but mitigated along with expertise. Additionally, after receiving training, the MBSR groups mindfulness and emotion regulation levels improved significantly, which were correlated with the EEG spectral changes in the theta, alpha, and low-beta bands. This study elaborated the neurophysiological correlates of mindfulness practices, suggesting that MBSR might function as a unique internal processing that involves increased vigilant capability and induces alterations similar to other cognitive training.

neuroscience↗