Zebrafish neuromesodermal progenitors undergo a critical state transition in vivo

The transition state model of cell differentiation proposes that a transient win-dow of gene expression stochasticity precedes entry into a differentiated state. Here, we assess this theoretical model in zebrafish neuromesodermal progeni-tors (NMps) in vivo during late somitogenesis stages. We observed an increase in gene expression variability at the 24 somite stage (24ss) before their differen-tiation into spinal cord and paraxial mesoderm. Analysis of a published 18ss scRNA-seq dataset showed that the NMp population is noisier than its deriva-tives. By building in silico composite gene expression maps from image data, we assigned an 'NM index' to in silico NMps based on the expression of neural and mesodermal markers and demonstrated that cell population heterogeneity peaked at 24ss. Further examination revealed cells with gene expression profiles incongruent with their prospective fate. Taken together, our work supports the transition state model within an endogenous cell fate decision making event.

Automated summary

This study supports the existence of the transition state model of cell differentiation by observing gene expression variability in zebrafish neuromesodermal progenitors. The results show that there is a transient window of gene expression stochasticity before entry into a differentiated state, and cell population heterogeneity peaks during this period.