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

Adriano Bolondi, Benjamin K. Law, Helene Kretzmer, Seher Ipek Gassaloglu, René Buschow, Christina Riemenschneider, Dian Yang, Maria Walther, Jesse V. Veenvliet, Alexander Meissner, Zachary D. Smith, Michelle M. Chan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1489-1505.e14
JournalDevelopmental cell
Volume59
Issue number12
DOIs
StatePublished - Jun 17 2024

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Keywords

  • cell plasticity
  • embryonic development
  • lineage tracing
  • molecular recording
  • morphogenesis
  • neuro-mesodermal progenitor dynamics
  • single-cell phylogenies
  • stem cell embryoids

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