Oral Presentation Hunter Cell Biology Meeting 2025

Spatiotemporal identification and lineage tracing of Mesendoderm progenitor cells in mammalian embryo (120066)

V. Pragathi Masamsetti 1 , Nazmus Salehin 1 , Hani Jieun Kim 2 , Nicole Santucci 1 , Megan Weatherstone 1 , Nadar Aryamanesh 1 , Pierre Osteil 1 , Pengyi Yang 2 , Patrick Tam 1
  1. Embryology Unit, Children's Medical Research Institute, Westmead, NSW, Australia
  2. Computational Systems Biology Group, Children's Medical Research Institute, Westmead, NSW, Australia

The cells of an early embryo are multipotent, hence capable of contributing to a multitude of cell types in the body. As the development progresses, these progenitor cells become restricted in lineage competency for germ layer derivatives. At gastrulation, the pluripotent epiblast cells are allocated to the progenitors for tissues of the ectoderm, mesoderm, and endoderm1. However, when and whereabouts of the allocation of the progenitors and their developmental trajectory towards germ layer tissues are not well understood. Previous studies of nematode and zebrafish embryos identified a subset of progenitors that display dual propensity of differentiation to mesoderm and endoderm2. In this study, we identified the location of the putative mesendoderm progenitors in the germ layers of the mouse embryo and characterised the molecular signature of these bipotential progenitors by single-cell transcriptomic analysis3. These progenitor cells are localized to the posterior epiblast, primitive streak and nascent mesoderm of mid-streak (E7.0) to late-streak stage (E7.5) embryos. Lineage tracing in vivo revealed that putative mesendoderm progenitors contribute descendants to the definitive endoderm and the axial mesendoderm of E7.75 embryos and to the endoderm of the foregut and hindgut of the E8.5-8.75 embryos. These bipotential mesendoderm progenitors were also identified in early in-vitro human embryo models. We are currently investigating the single cell gene expression and single cell ATAC-seq data of the gastrulating mouse embryos to further understand the progenitor gene signature and regulation. Understanding the origin, spatiotemporal distribution, molecular signature and lineage specification of the bipotential progenitors enriches our mechanistic understanding of the allocation of the tissue progenitors to germ layer derivatives in early development. This knowledge will be applicable for efficient generation of biologically relevant cell types in tissue engineering.

  1. Wang, R., et al., Time space and single-cell resolved tissue lineage trajectories and laterality of body plan at gastrulation. Nat Commun, 2023. 14(1): p. 5675.
  2. Maduro, M.F., et al., Restriction of mesendoderm to a single blastomere by the combined action of SKN-1 and a GSK-3beta homolog is mediated by MED-1 and -2 in C. elegans. Mol Cell, 2001. 7(3): p. 475-85.
  3. Masamsetti, V.P., et .al., Characterization of the mesendoderm progenitors in the gastrulating mouse embryo. BiorXiv 2024 https://doi.org/10.1101/2024.04.28.591221