Biology subjects

Schröter, C.

Publications and source records attributed to Schröter, C..

4 recordsLinked to original sources

bioRxiv2024

Single-cell multiome uncovers differences in glycogen metabolism underlying species-specific speed of development

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.

developmental biology↗

bioRxiv2024

Med12 cooperates with multiple differentiation signals to enhance embryonic stem cell plasticity

Cell differentiation results from coordinated changes in gene transcription in response to combinations of signals. FGF, Wnt, and mTOR signals regulate the differentiation of pluripotent mammalian cells towards embryonic and extraembryonic lineages, but how these signals cooperate with general transcriptional regulators is not fully resolved. Here, we report a genome-wide CRISPR screen that reveals both signaling components and general transcriptional regulators for differentiation-associated gene expression in mESCs. Focusing on the Mediator subunit Med12 as one of the strongest hits in the screen, we show that it regulates gene expression in parallel to FGF and mTOR signals. Loss of Med12 is compatible with differentiation along both the embryonic epiblast and the extraembryonic primitive endoderm lineage, but impairs pluripotency gene expression and slows down transitions between pluripotency states. These findings suggest that Med12 helps pluripotent cells to efficiently execute transcriptional changes during differentiation, thereby modulating the effects of a broad range of signals.

cell biology↗

bioRxiv2020

Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells

Signal transduction networks process extracellular signals to guide cell fate decisions such as to divide, differentiate, or die. These networks can generate characteristic dynamic activities that are shaped by their cell-type specific architecture. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, the dynamic activity of the FGF/ERK signaling network in this context remains unexplored. Here we use live cell sensors in wild type and Fgf4 mutant mouse embryonic stem cells to measure ERK dynamic activity in single cells, in response to defined ligand concentrations. We find that ERK activity oscillates in embryonic stem cells. Single cells can transit between oscillatory and non-oscillatory behavior, leading to heterogeneous dynamic activities in the population. Oscillations become more prevalent with increasing FGF4 dose, while maintaining a robust characteristic timescale. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells.

developmental biology↗

bioRxiv2020

Cell-cell communication through FGF4 generates and maintains robust proportions of differentiated cell fates in embryonic stem cells

During embryonic development and tissue homeostasis, reproducible proportions of differentiated cell types are specified from populations of multipotent precursor cells. Molecular mechanisms that enable both robust cell type proportioning despite variable initial conditions in the precursor cells, as well as the re-establishment of these proportions upon perturbations in a developing tissue remain to be characterized. Here we report that the differentiation of robust proportions of epiblast-like and primitive endoderm-like cells in mouse embryonic stem cell cultures emerges at the population level through cell-cell communication via a short-range FGF4 signal. We characterize the molecular and dynamical properties of the communication mechanism, and show how it controls both robust cell type proportioning from a wide range of experimentally controlled initial conditions, as well as the autonomous re-establishment of these proportions following the isolation of one cell type. The generation and maintenance of reproducible proportions of discrete cell types is a new function for FGF signaling that may operate in a range of developing tissues.

developmental biology↗