SUN, X. | bioRxiv Science

bioRxiv2026

Joint recording of past and present transcriptomes reconstructs single-cell trajectories

Tracing molecular cell state transitions through development, homeostasis and disease is still beyond reach at single-cell resolution. We present scReMeMber-Seq, a methylation-based cell-memory recorder connecting past transcriptional states with present transcriptome and DNA methylome in individual cells. scReMeMber-Seq leverages pulse induction of DCM-Polr2b (TimeMachine) and single-cell methylome-transcriptome (scMT) sequencing for endpoint readout. In mouse neural stem cells (NSCs) and pancreatic organoids, single-cell DCM methylation profiles (scDCMome) accurately discriminate cell types. Over time, scDCMome also record NSC quiescence-activation state changes across multiple cell divisions. In zebrafish embryos, scDCMome resolve individual transcriptional trajectories from progenitor to neuron. Together, scReMeMber-Seq enables real time reconstruction of cellular trajectories, connecting past and present molecular states in single cells, at genome scale, across experimental systems, in vitro and in vivo.

neuroscience↗

bioRxiv2024

Dimorphic Neural Network Architecture Prioritizes Sexual-related Behaviors in Male C.elegans

Neural network architecture determines its functional output. However, the detailed mechanisms are not well characterized. In this study, we focused on the neural network architectures of male and hermaphrodite C. elegans and the association with sexually dimorphic behaviors. We applied graph theory and computational neuroscience methods to systematically discern the features of these two neural networks. Our findings revealed that a small percentage of sexual-specific neurons exerted dominance throughout the entire male neural net-work, suggesting males prioritized sexual-related behavior outputs. Based on the structural and dynamical characteristics of two complete neural networks, sub-networks containing sex-specific neurons and their immediate neighbors, or sub-networks exclusively comprising sex-shared neurons, we predicted dimorphic behavioral outcomes for males and hermaphrodites. To verify the prediction, we performed behavioral and calcium imaging experiments and dissected a circuit that is specific for the increased spontaneous local search in males for mate-searching. Our research sheds light on the neural circuits that underlie sexually dimorphic behaviors in C. elegans, and provides significant insights into the inter-connected relationship between network architecture and functional outcomes at the whole-brain level.

neuroscience↗