Dataset Information

Integrative Functional, Molecular, and Transcriptomic Analyses of Altered Intrinsic Timescale Gradient in Depression.

ABSTRACT: The pathophysiology and pharmacology of depression are hypothesized to be related to the imbalance of excitation-inhibition that gives rise to hierarchical dynamics (or intrinsic timescale gradient), further supporting a hierarchy of cortical functions. On this assumption, intrinsic timescale gradient is theoretically altered in depression. However, it remains unknown. We investigated altered intrinsic timescale gradient recently developed to measure hierarchical brain dynamics gradient and its underlying molecular architecture and brain-wide gene expression in depression. We first presented replicable intrinsic timescale gradient in two independent Chinese Han datasets and then investigated altered intrinsic timescale gradient and its possible underlying molecular and transcriptional bases in patients with depression. As a result, patients with depression showed stage-specifically shorter timescales compared with healthy controls according to illness duration. The shorter timescales were spatially correlated with monoamine receptor/transporter densities, suggesting the underlying molecular basis of timescale aberrance and providing clues to treatment. In addition, we identified that timescale aberrance-related genes ontologically enriched for synapse-related and neurotransmitter (receptor) terms, elaborating the underlying transcriptional basis of timescale aberrance. These findings revealed atypical timescale gradient in depression and built a link between neuroimaging, transcriptome, and neurotransmitter information, facilitating an integrative understanding of depression.

SUBMITTER: Han S

PROVIDER: S-EPMC8891525 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Integrative Functional, Molecular, and Transcriptomic Analyses of Altered Intrinsic Timescale Gradient in Depression.

Han Shaoqiang S Zheng Ruiping R Li Shuying S Zhou Bingqian B Jiang Yu Y Wang Caihong C Wei Yarui Y Pang Jianyue J Li Hengfen H Zhang Yong Y Chen Yuan Y Cheng Jingliang J

Frontiers in neuroscience 20220217

The pathophysiology and pharmacology of depression are hypothesized to be related to the imbalance of excitation-inhibition that gives rise to hierarchical dynamics (or intrinsic timescale gradient), further supporting a hierarchy of cortical functions. On this assumption, intrinsic timescale gradient is theoretically altered in depression. However, it remains unknown. We investigated altered intrinsic timescale gradient recently developed to measure hierarchical brain dynamics gradient and its ...[more]

PMID: 35250462

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Project description:BackgroundThe global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized.MethodsBased on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors.ResultsOur analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings.ConclusionsThis study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Dataset Information

Integrative Functional, Molecular, and Transcriptomic Analyses of Altered Intrinsic Timescale Gradient in Depression.

Publications

Integrative Functional, Molecular, and Transcriptomic Analyses of Altered Intrinsic Timescale Gradient in Depression.

Similar Datasets

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