Joint recording of past and present transcriptomes reconstructs single-cell trajectories
- 1Institut Pasteur and CNRS UMR3738, Paris, France
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.
Related
- CardioChrom Reconstructs the Human Cardiac Virtual Epigenome from Single-Nucleus Transcriptomes
- scMTG reconstructs single-cell temporal dynamics with Markov transition generators
- RECON infers regions of interest from H&E images and reconstructs whole-slide molecular profiles at single-cell resolution
- Decoding Cell-level Circadian Phase and Rhythm-state Remodeling in Single-cell Transcriptomes With scRhythmBayes
- Recording proteome dynamics in the late-stage embryo at hour-timescale, spatial, and single-cell resolution with MEMBRYO
BibTeX
@misc{aydin2026joint,
title = {{Joint recording of past and present transcriptomes reconstructs single-cell trajectories}},
author = {Z. AYDIN and S. OVCHINNIKOVA and I. A. UNTERWEGER and S. CERRIZUELA and N. PONT and V. WUST and R. BOERS and K. ZIRNGIBL and O. CAN and M. SPATUZZI and T. TRABOULSI and X. SUN and A. KORKMAZ and S. ORTICA and T. FOLEY and K. VOLK and S. KLEBER and A. SANZ-MOREJON and M. Hasan and J. Gribnau and S. ANDERS and A. MARTIN-VILLALBA and L. BALLY-CUIF},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.755048},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.755048v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Joint recording of past and present transcriptomes reconstructs single-cell trajectories
AU - Z. AYDIN
AU - S. OVCHINNIKOVA
AU - I. A. UNTERWEGER
AU - S. CERRIZUELA
AU - N. PONT
AU - V. WUST
AU - R. BOERS
AU - K. ZIRNGIBL
AU - O. CAN
AU - M. SPATUZZI
AU - T. TRABOULSI
AU - X. SUN
AU - A. KORKMAZ
AU - S. ORTICA
AU - T. FOLEY
AU - K. VOLK
AU - S. KLEBER
AU - A. SANZ-MOREJON
AU - M. Hasan
AU - J. Gribnau
AU - S. ANDERS
AU - A. MARTIN-VILLALBA
AU - L. BALLY-CUIF
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.755048
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.755048v1
AB - 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.
ER -