Biology subjects

Zhou, J. H.

Publications and source records attributed to Zhou, J. H..

21 records · Page 2Linked to original sources

bioRxiv2022

Stage dependent differential influence of metabolic and structural networks on memory across Alzheimer's disease continuum

BackgroundLarge-scale neuronal network breakdown underlies memory impairment in Alzheimers disease (AD). However, the differential trajectories of the relationships between network organization and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship. Methods708 participants from the Alzheimers Disease Neuroimaging Initiative were studied. Individual-level structural and metabolic covariance scores in higher-level cognitive and hippocampal networks were derived from magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography using seed-based partial least square analyses. The non-linear associations between network scores and memory across cognitive stages in each pathology group were examined using sparse varying coefficient modelling. ResultsWe showed that the associations of memory with structural and metabolic networks in the hippocampal and default mode regions exhibited pathology-dependent differential trajectories across cognitive stages using sparse varying coefficient modelling. In amyloid pathology group, there was an early influence of hippocampal structural network deterioration on memory impairment in the preclinical stage, and a biphasic influence of the angular gyrus-seeded default mode network metabolism on memory in both preclinical and dementia stages. In non-amyloid pathology groups, in contrast, the trajectory of the hippocampus-memory association was opposite and weaker overall, while no metabolism covariance networks were related to memory. Key findings were replicated in a larger cohort of 1280 participants. ConclusionsOur findings highlight potential windows of early intervention targeting network breakdown at the preclinical AD stage.

neuroscience↗

bioRxiv2019

Genome reorganization prior to mitosis shapes the generation of adaptive immunity

During cellular differentiation chromosome conformation is altered to support the lineage-specific transcriptional programs required for cell identity. When these changes occur in relation to cell cycle, division and time is unclear. Here we followed B lymphocytes as they differentiated from a naive, quiescent state into antibody secreting plasma cells. Unexpectedly, we found that gene-regulatory chromosome reorganization occurred prior to the first division, in late G1 phase and that this configuration is maintained as the cells rapidly cycle during clonal expansion. A second wave of architectural changes also occurred later as cells differentiated into plasma cells and this was associated with increased time in G1 phase. These data provide an explanation for how lymphocyte fate is imprinted prior to the first division and suggest that chromosome reconfiguration is spatiotemporally separated from DNA replication and mitosis to ensure the implementation of a gene regulatory program that controls the differentiation process required for the generation of immunity.\n\nOne Sentence SummaryDiscrete waves of genome reorganization, spatiotemporally separated from DNA replication and mitosis, control cell differentiation.

genomics↗

bioRxiv2019

p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes

The transcription factor p63 regulates epidermal genes and the enhancer landscape in skin keratinocytes. Its molecular function in controlling the chromatin structure is however not yet completely understood. Here we integrated multi-omics profiles, including the transcriptome, transcription factor DNA-binding and chromatin accessibility, in skin keratinocytes isolated from EEC syndrome patients carrying p63 mutations to examine the role of p63 in shaping the chromatin architecture. We found decreased chromatin accessibility in p63- and CTCF-bound open chromatin regions that potentially contributed to gene deregulation in mutant keratinocytes. Cooperation of p63 and CTCF seemed to assist chromatin interactions between p63-bound enhancers and gene promoters in skin keratinocytes. Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genome organizer CTCF in the three-dimensional chromatin space to regulate the transcription program important for the proper cell identity.

genomics↗