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Biology subjects

Chi, N.

Publications and source records attributed to Chi, N..

3 recordsLinked to original sources

NeuroPilot: Longitudinal intravital neural imaging across scales and modalities through an agentic platform

Longitudinal intravital imaging is essential for understanding how neural populations evolve across behavioral states, yet converting large-scale recordings into biological insight remains a fundamental challenge because neural signals are degraded by noise, non-rigid motion, and heterogeneous recording conditions. Here we introduce NeuroPilot, an agentic framework that transforms neural imaging analysis into a closed-loop, context-aware process, integrating a multimodal large language model with callable computational imaging modules to adaptively coordinate workflows from raw recordings to population-level readouts. Across heterogeneous imaging and experimental regimes, NeuroPilot restores motion-degraded recordings and supports consistent neural signal recovery, detection, and tracking in challenging deep-brain, freely moving, and longitudinal settings. These enable neuronal population tracking across spinal stimulation paradigms, deep-brain imaging, and continuous 24-hour mPFC recordings aligned with spontaneous sleep-wake behavior. By converting heterogeneous intravital recordings into stable population activity maps, NeuroPilot supports behavioral decoding and reveals structured neural dynamics across behavioral states and transitions. NeuroPilot establishes a scalable agentic paradigm for neural imaging analysis, expanding experimental access to the measurement, visualization, and interpretation of neural population activity.

neuroscience↗

3D Chromatin Architecture Remodeling during Human Cardiomyocyte Differentiation Reveals A Novel Role of HERV-H In Demarcating Chromatin Domains

Dynamic restructuring of chromatin architecture has been implicated in cell-type specific gene regulatory programs; yet, how chromatin remodels during lineage specification remains to be elucidated. Through interrogating chromatin reorganization during human cardiomyocyte differentiation, we uncover dynamic chromatin interactions between genes and distal regulatory elements harboring noncoding variants associated with adult and congenital heart diseases. Unexpectedly, we also discover a new class of human pluripotent stem cell (PSC)-specific topologically associating domains (TAD) that are created by the actively transcribed endogenous retrotransposon HERV-H. Deletion or silencing of specific HERV-H elements eliminates corresponding TAD boundaries, while de novo insertion of HERV-H can introduce new chromatin domain boundaries in human PSCs. Furthermore, comparative analysis of chromatin architecture in other species that lack HERV-H sequences supports a role for actively transcribed HERV-H in demarcating human PSC-specific TADs. The biological role of HERV-H is further underscored by the observation that deletion of a specific HERV-H reduces transcription of genes upstream and facilitates cell differentiation. Overall, our results highlight a previously unrecognized role for retrotransposons in restructuring genome architecture in the human genome and delineate dynamic gene regulatory networks during cardiomyocyte development that inform how non-coding genetic variants contribute to human heart diseases.

genomics↗

Diverse yet highly selective interorgan crosstalk mechanisms shape the bodywide transcriptome landscape

The cardiovascular system facilitates body-wide distribution of oxygen, a vital process for development and survival of virtually all vertebrates. However, zebrafish, a vertebrate model organism, appears to form organs and survive mid-larval periods without the functional cardiovascular system. Despite such dispensability, it is the first organ to develop. Such enigma prompted us to hypothesize yet other cardiovascular functions that are important for developmental and/or physiological processes. Hence, systematic cellular ablations and functional perturbations are performed on zebrafish cardiovascular system to gain comprehensive and body-wide understanding of such functions and to elucidate underlying mechanisms. This approach identifies a set of organ-specific genes, each implicated for important functions. The study also unveils distinct cardiovascular mechanisms, each differentially regulating their expressions in organ-specific and oxygen-independent manners. Such mechanisms are mediated by organ-vessel interactions, circulation-dependent signals, and circulation-independent beating-heart-derived signals. Hence, a comprehensive and body-wide functional landscape of the cardiovascular system reported herein may provide a clue as to why it is the first organ to develop. Furthermore, the dataset herein could serve as a resource for the study of organ development and function.\n\nSUMMARY STATEMENTThe body-wide landscape of the cardiovascular functions during development is reported. Such landscape may provide a clue as to why the cardiovascular system is the first organ to develop.

systems biology↗