Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids DOI Open Access
Kyoung Jo,

Zong-Yuan Liu,

Gauri Patel

et al.

Published: Nov. 8, 2024

The role of FGF is the least understood morphogens driving mammalian gastrulation. Here we investigated function in a stem cell model for human gastrulation known as 2D gastruloid. We found ring FGF-dependent ERK activity that closely follows emergence primitive streak (PS)-like cells but expands further inward. showed this pattern required PS-like differentiation and loss upon receptor inhibition can be rescued by directly activating ERK. demonstrated ERK-ring depends on localized activation basally receptors (FGFR) endogenous gradients. confirm extend previous studies analyzing expression pathway components, showing main to FGFR1 key ligands FGF2/4/17, similar monkey embryo different from mouse. In situ hybridization scRNA-seq revealed FGF4 FGF17 colocalize with PS marker TBXT only maintained nascent mesoderm endoderm. reduction both reduced their derivatives, indicating overlapping function. Thus, have identified previously unknown signaling gastruloids possibly embryo, driven mechanism where signal through induce cells.

Language: Английский

Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling DOI Creative Commons
Kristina S. Stapornwongkul, Elisa Hahn, Patryk Poliński

et al.

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive of glycolytic activity in regulating signaling involved mesoderm and endoderm specification. Using a mouse stem (mESC)-based vitro model for gastrulation, found that glycolysis inhibition increases ectodermal fates at the expense mesodermal endodermal lineages. We this relationship is dose dependent, enabling metabolic control germ layer proportions through exogenous glucose levels. further show acts as upstream regulator Nodal Wnt its on specification be decoupled from effects growth. Finally, confirm generality our findings using human gastrulation model. Our work underscores dependence conditions provides mechanistic insight into nutritional regulation decision-making.

Language: Английский

Citations

0
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids DOI
Kyoung Jo,

Zong-Yuan Liu,

Gauri Patel

et al.

Published: July 11, 2024

The role of FGF is the least understood morphogens driving mammalian gastrulation. Here we investigated function in a stem cell model for human gastrulation known as 2D gastruloid. We found ring FGF-dependent ERK activity that closely follows emergence primitive streak (PS)-like cells but expands further inward. showed this pattern required PS-like differentiation and loss upon receptor inhibition can be rescued by directly activating ERK. demonstrated ERK-ring depends on localized activation basally receptors (FGFR) endogenous gradients. confirm extend previous studies analyzing expression pathway components, showing main to FGFR1 key ligands FGF2/4/17, similar monkey embryo different from mouse. In situ hybridization scRNA-seq revealed

Language: Английский

Citations

1
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids DOI Open Access
Kyoung Jo,

Zong-Yuan Liu,

Gauri Patel

et al.

Published: Nov. 8, 2024

The role of FGF is the least understood morphogens driving mammalian gastrulation. Here we investigated function in a stem cell model for human gastrulation known as 2D gastruloid. We found ring FGF-dependent ERK activity that closely follows emergence primitive streak (PS)-like cells but expands further inward. showed this pattern required PS-like differentiation and loss upon receptor inhibition can be rescued by directly activating ERK. demonstrated ERK-ring depends on localized activation basally receptors (FGFR) endogenous gradients. confirm extend previous studies analyzing expression pathway components, showing main to FGFR1 key ligands FGF2/4/17, similar monkey embryo different from mouse. In situ hybridization scRNA-seq revealed FGF4 FGF17 colocalize with PS marker TBXT only maintained nascent mesoderm endoderm. reduction both reduced their derivatives, indicating overlapping function. Thus, have identified previously unknown signaling gastruloids possibly embryo, driven mechanism where signal through induce cells.

Language: Английский

Citations

0
Endogenous FGFs drive ERK-dependent cell fate patterning in 2D human gastruloids DOI Open Access
Kyoung Jo,

Zong-Yuan Liu,

Gauri Patel

et al.

Published: Nov. 8, 2024

The role of FGF is the least understood morphogens driving mammalian gastrulation. Here we investigated function in a stem cell model for human gastrulation known as 2D gastruloid. We found ring FGF-dependent ERK activity that closely follows emergence primitive streak (PS)-like cells but expands further inward. showed this pattern required PS-like differentiation and loss upon receptor inhibition can be rescued by directly activating ERK. demonstrated ERK-ring depends on localized activation basally receptors (FGFR) endogenous gradients. confirm extend previous studies analyzing expression pathway components, showing main to FGFR1 key ligands FGF2/4/17, similar monkey embryo different from mouse. In situ hybridization scRNA-seq revealed FGF4 FGF17 colocalize with PS marker TBXT only maintained nascent mesoderm endoderm. reduction both reduced their derivatives, indicating overlapping function. Thus, have identified previously unknown signaling gastruloids possibly embryo, driven mechanism where signal through induce cells.

Language: Английский

Citations

0