Year: 2026
Type: preprint
Abstract: ABSTRACT 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 .
Authors: Zeynep Aydin, Svetlana Ovchinnikova, Iris A Unterweger, Santiago Cerrizuela, Naomie Pont, Valentin Wüst, Ruben Boers, Katharina Zirngibl, Özgür Can, Matteo Spatuzzi, Tatiana Traboulsi, Xiaoyu Sun, Aylin Korkmaz, Sara Ortica, Tanya Foley, Katrin Volk, Susanne Kleber, Andres Sanz-Morejón, Milena Hasan, Joost Gribnau, Simon Anders, Ana Martin-Villalba, Laure Bally-Cuif
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1692958442, GRK 2727: Checkpoints der angeborenen Immunität bei Krebs und Gewebeschaden (InCheck), Pilotage et gouvernance du programme Cell ID, Accessing individual Cell Identity in their native spatial context: The revolution of single cell and spatially resolved multi-omics., Training and career development & Innovation, G5284521312, G5839140157, G6461157608, Data Integration and Medical Applications, G7853904736, dedicated experimental systems, Stem Cells in Regenerative Biology and Medicine
OpenAlex ID: W7214929657