Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking

McNamara, Harold M.; Solley, Sabrina C.; Adamson, Britt; Chan, Michelle M.; Toettcher, Jared E.

doi:10.1038/s41556-024-01521-9

Cited by 3 publications

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

The lives of cells, recorded

Askary,

Chen,

Choi

et al. 2024

Nat Rev Genet

View full text Add to dashboard Cite

A paradigm for biology is emerging in which cells can be genetically programmed to write their histories into their own genomes. These records can subsequently be read, and the cellular histories reconstructed, which for each cell could include a record of its lineage relationships, extrinsic influences, internal states and physical locations, over time. DNA recording has the potential to transform the way that we study developmental and disease processes. Recent advances in genome engineering are driving the development of systems for DNA recording, and meanwhile single-cell and spatial omics technologies increasingly enable the recovery of the recorded information. Combined with advances in computational and phylogenetic inference algorithms, the DNA recording paradigm is beginning to bear fruit. In this Perspective, we explore the rationale and technical basis of DNA recording, what aspects of cellular biology might be recorded and how, and the types of discovery that we anticipate this paradigm will enable. SectionsIntroduction Recording cellular histories Applications of DNA-based recording Practical challenges for DNA-based recording Emerging opportunities Conclusions

show abstract

The lives of cells, recorded

Askary,

Chen,

Choi

et al. 2024

Nat Rev Genet

View full text Add to dashboard Cite

show abstract

Morphogenetic constrains in the development of gastruloids: implications for mouse gastrulation

Fiuza,

Bonavia,

Pascual-Mas

et al. 2024

Preprint

View full text Add to dashboard Cite

Mammalian embryonic size is tightly controlled with checkpoints and compensatory mechanisms correcting size defects. Here, we take advantage of gastruloids, a stem cell embryoid system not subject to most size controls, to study the role of size in emergent properties of mammalian embryogenesis. We report that gastruloids exhibit robust morphology and transcriptional profiles within a size range. However, size affects the dynamics, and, outside a range of robust morphogenesis, the precision of anterior-posterior (AP) axial elongation. Gastruloid axial elongation exhibits active cellular contractility, requires planar cell polarity (PCP), adhesion and cell-cell contact remodelling. Smaller gastruloids initiate elongation earlier, correlated with an earlier Brachyury polarisation. Brachyury expression increases tissue fluidity. Axis formation is regulated by the balance of Brachyury multifoci coalescence and the timing of initiation of the elongation programme. Sizes beyond the robust range can modify relative tissue composition. Very small aggregates have increased neural fate bias, accompanied by a loss of paraxial mesoderm mediated by differences in Nodal signalling activity.

show abstract

Early autonomous patterning of the anteroposterior axis in gastruloids

Anlaş,

Gritti,

Nakaki

et al. 2024

Development

View full text Add to dashboard Cite

Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates – such as gastruloids – can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect the dynamics of AP axis establishment in mouse gastruloids, particularly before external Wnt stimulation. Through single-cell RNA sequencing, we identify key cell state transitions and the molecular signatures of T+ and T− populations underpinning AP polarization. We also show that this process is robust to modifications of aggregate size. Finally, transcriptomic comparison with the mouse embryo indicates that gastruloids develop similar mesendodermal cell types, despite initial differences in their primed pluripotent populations, which adopt a more mesenchymal state in lieu of an epiblast-like transcriptome. Hence, our findings suggest the possibility of alternate ESC states in vivo and in vitro that can converge onto similar cell fates.

show abstract

Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking

Cited by 3 publications

References 55 publications

The lives of cells, recorded

The lives of cells, recorded

Morphogenetic constrains in the development of gastruloids: implications for mouse gastrulation

Early autonomous patterning of the anteroposterior axis in gastruloids

Contact Info

Product

Resources

About