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PreprintCC BY-NC-NDbioRxiv

Recording proteome dynamics in the late-stage embryo at hour-timescale, spatial, and single-cell resolution with MEMBRYO

1 more authors
  1. 1Max Planck Institute for Molecular Genetics

Abstract

Cell fate during development is directed by new gene expression states that replace prior ones. When and where a protein is first translated, and how long it will remain in the cell, dictate the timing and extent of a gene's phenotypic effect. Accessing protein synthesis and turnover information in the rapidly developing embryo remains a major challenge. Here we present MEMBRYO: a method for continuous stable isotope labeling (SILAC) of newly synthesized proteins throughout the live embryo at the hour-timescales of developmental phenotypes. We extend embryo culture into the late stages of organogenesis, thereby accessing the proteome of neurogenesis in the forebrain ex utero. Variations in protein synthesis and turnover activity lead to expression patterns that diverge from the corresponding transcripts, impacting molecular pathways and key milestones of cortical neuron differentiation. The high labeling depth enabled both spatial and single-cell SILAC proteomics analysis of cortical cells, revealing distinct layers of post-transcriptional gene expression regulation in progenitors and neurons. By continuous metabolic labeling in the live embryo, MEMBRYO tracks the past, present, and future of the developmental proteome.

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BibTeX
@misc{couceiglesias2026recording,
  title = {{Recording proteome dynamics in the late-stage embryo at hour-timescale, spatial, and single-cell resolution with MEMBRYO}},
  author = {M. Couce-Iglesias and E. Oliani and R. Kerridge and F. Mutschler and D. S. Valdes and A. S. Welter and B. Lukaszewska-McGreal and D. Meierhofer and K. Imami and E. F. Fornasiero and F. Coscia and M. Selbach and M. L. Kraushar},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.21.753234},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753234v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Recording proteome dynamics in the late-stage embryo at hour-timescale, spatial, and single-cell resolution with MEMBRYO
AU  - M. Couce-Iglesias
AU  - E. Oliani
AU  - R. Kerridge
AU  - F. Mutschler
AU  - D. S. Valdes
AU  - A. S. Welter
AU  - B. Lukaszewska-McGreal
AU  - D. Meierhofer
AU  - K. Imami
AU  - E. F. Fornasiero
AU  - F. Coscia
AU  - M. Selbach
AU  - M. L. Kraushar
PY  - 2026
DA  - 2026/09/21
PB  - bioRxiv
DO  - 10.64898/2026.09.21.753234
UR  - https://www.biorxiv.org/content/10.64898/2026.09.21.753234v1
AB  - Cell fate during development is directed by new gene expression states that replace prior ones. When and where a protein is first translated, and how long it will remain in the cell, dictate the timing and extent of a gene's phenotypic effect. Accessing protein synthesis and turnover information in the rapidly developing embryo remains a major challenge. Here we present MEMBRYO: a method for continuous stable isotope labeling (SILAC) of newly synthesized proteins throughout the live embryo at the hour-timescales of developmental phenotypes. We extend embryo culture into the late stages of organogenesis, thereby accessing the proteome of neurogenesis in the forebrain ex utero. Variations in protein synthesis and turnover activity lead to expression patterns that diverge from the corresponding transcripts, impacting molecular pathways and key milestones of cortical neuron differentiation. The high labeling depth enabled both spatial and single-cell SILAC proteomics analysis of cortical cells, revealing distinct layers of post-transcriptional gene expression regulation in progenitors and neurons. By continuous metabolic labeling in the live embryo, MEMBRYO tracks the past, present, and future of the developmental proteome.
ER  -