Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Adriano Bolondi - , Max Planck Institute for Molecular Genetics (Author)
  • Benjamin K. Law - , Princeton University (Author)
  • Helene Kretzmer - , Max Planck Institute for Molecular Genetics (Author)
  • Seher Ipek Gassaloglu - , Max Planck Institute for Molecular Genetics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • René Buschow - , Max Planck Institute for Molecular Genetics (Author)
  • Christina Riemenschneider - , Max Planck Institute for Molecular Genetics (Author)
  • Dian Yang - , Columbia University (Author)
  • Maria Walther - , Max Planck Institute for Molecular Genetics (Author)
  • Jesse V. Veenvliet - , Max Planck Institute of Molecular Cell Biology and Genetics, TUD Dresden University of Technology, Center for Systems Biology Dresden (CSBD), Clusters of Excellence PoL: Physics of Life (Author)
  • Alexander Meissner - , Max Planck Institute for Molecular Genetics, Free University of Berlin (Author)
  • Zachary D. Smith - , Yale University (Author)
  • Michelle M. Chan - , Princeton University (Author)

Abstract

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.

Details

Original languageEnglish
Pages (from-to)1489-1505.e14
JournalDevelopmental cell
Volume59
Issue number12
Publication statusPublished - 17 Jun 2024
Peer-reviewedYes

External IDs

PubMed 38579718

Keywords

Keywords

  • cell plasticity, embryonic development, lineage tracing, molecular recording, morphogenesis, neuro-mesodermal progenitor dynamics, single-cell phylogenies, stem cell embryoids, Somites/cytology, Embryonic Development, Mouse Embryonic Stem Cells/cytology, Cell Lineage, Animals, Gene Expression Regulation, Developmental, Mice, Cell Differentiation, Mesoderm/cytology