Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments

Alwyn Dady (Lead / Corresponding author), Lindsay Davidson, Pamela Halley, Kate Storey (Lead / Corresponding author)

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Abstract

Species-specific differentiation pace in-vitro indicates that some aspects of neural differentiation are governed by cell intrinsic properties. Here we describe a novel in-vitro human neural-rosette assay that recapitulates dorsal spinal cord differentiation but proceeds more rapidly than in the human embryo, suggesting that it lacks endogenous signalling dynamics. To test whether in-vitro conditions represent an intrinsic differentiation pace, human iPSC-derived neural rosettes were challenged by grafting into the faster differentiating chicken embryonic neural tube iso-chronically, or hetero-chronically into older embryos. In both contexts in-vitro differentiation pace was initially unchanged, while long-term analysis revealed iso-chronic slowed and hetero-chronic conditions promoted human neural differentiation. Moreover hetero-chronic conditions did not alter the human neural differentiation programme, which progressed to neurogenesis, while the host embryo advanced into gliogenesis. This study demonstrates that intrinsic properties limit human differentiation pace, and that timely extrinsic signals are required for progression through an intrinsic human neural differentiation programme.
Original languageEnglish
Article numbere67283
JournaleLife
Volume11
Early online date21 Feb 2022
DOIs
Publication statusPublished - Feb 2022

Keywords

  • Human pluripotent cells
  • Human spinal cord development
  • Neural differentiation timing
  • Xenografting

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