Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
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.
Authors 11
-
Alexandra de la Porte Aachen Division of Cell Systems and Drug Safety Leiden Academic Centre for Drug Research
Affiliation as printed
Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University
Institute of Stem Cell Research
-
Max Planck Institute of Molecular Physiology
Affiliation as printed
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology
-
Technical University of Munich
Affiliation as printed
Institute of AI for Health
School of Life Sciences Weihenstephan, Technical University of Munich
-
Ludwig-Maximilians-Universität München
Affiliation as printed
Anthropology and Human Genomics, Faculty of Biology, Ludwig-Maximilians-Universität München
-
Affiliation as printed
Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Center
-
Affiliation as printed
Department of Clinical Genetics, Erasmus MC University Medical Center
-
Affiliation as printed
Department of Clinical Genetics, Erasmus MC University Medical Center
-
Ludwig-Maximilians-Universität München
Affiliation as printed
Anthropology and Human Genomics, Faculty of Biology, Ludwig-Maximilians-Universität München
-
Carsten Marr corresponding
Affiliation as printed
Institute of AI for Health
-
Christian J. Schröter corresponding
Max Planck Institute of Molecular Physiology
Affiliation as printed
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology
-
Micha Drukker corresponding Aachen Division of Cell Systems and Drug Safety Leiden Academic Centre for Drug Research
Leiden University · Erasmus MC
Affiliation as printed
Department of Clinical Genetics, Erasmus MC University Medical Center
Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University
Institute of Stem Cell Research
Cited by 1 stored of 1
1 result
No patents citing this paper on Lens.org (checked 2026-10-11).