2024/09/03 by Alexandra de la Porte, Julia Schröder, Moritz Thomas +9 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Single-cell and spatial transcriptomics #Pluripotent Stem Cells Research #Zebrafish Biomedical Research Applications
paper · pdf · doi:10.1101/2024.09.03.610938
Abstract Embryos from different mammalian species develop at characteristic timescales. These timescales are recapitulated during the differentiation of pluripotent stem cells in vitro . Specific genes and molecular pathways that modulate cell differentiation speed between mammalian species remain to be determined. Here we use single-cell multi-omic analysis of neural differentiation of mouse, cynomolgus and human pluripotent cells to identify regulators for differentiation speed. We demonstrate that species-specific transcriptome dynamics are mirrored at the chromatin level, but that the speed of neural differentiation is insensitive to manipulations of cell growth and cycling. Exploiting the single-cell resolution of our data, we identify glycogen storage levels regulated by UDP-glucose pyrophosphorylase 2 (UGP2) as a species-dependent trait of pluripotent cells, and show that lowered glycogen storage in UGP2 mutant cells is associated with accelerated neural differentiation. The control of energy storage could be a general strategy for the regulation of cell differentiation speed.