Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model DOI Creative Commons

Alba Villaronga-Luque,

Ryan Savill, Natalia López-Anguita

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Язык: Английский

Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids DOI Creative Commons
Chaitanya Dingare, Dominica Cao,

Jenny Yang

и другие.

Developmental Cell, Год журнала: 2024, Номер 59(12), С. 1523 - 1537.e6

Опубликована: Апрель 17, 2024

Patterning and growth are fundamental features of embryonic development that must be tightly coordinated. To understand how metabolism impacts early mesoderm development, we used mouse stem-cell-derived gastruloids, co-expressed glucose transporters with the mesodermal marker T/Bra. We found mimic, 2-deoxy-D-glucose (2-DG), blocked T/Bra expression abolished axial elongation in gastruloids. However, removal did not phenocopy 2-DG treatment despite a decline glycolytic intermediates. As can also act as competitive inhibitor mannose protein glycosylation, added together it could rescue specification both vivo vitro. further showed blocking production intracellular recycling abrogated specification. Proteomics analysis demonstrated reversed glycosylation Wnt pathway regulator, secreted frizzled receptor Frzb. Our study controls

Язык: Английский

Процитировано

18
Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model DOI Creative Commons

Alba Villaronga-Luque,

Ryan Savill, Natalia López-Anguita

и другие.

Cell stem cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Язык: Английский

Процитировано

2