In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between DOI Creative Commons
Theodora M. Stougiannou, Konstantinos Christodoulou, Dimos Karangelis

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2714 - 2714

Опубликована: Ноя. 27, 2024

Cardiovascular disease comprises a group of disorders affecting or originating within tissues and organs the cardiovascular system; most, if not all, will eventually result in cardiomyocyte dysfunction death, negatively impacting cardiac function. Effective models are thus important for understanding crucial aspects progression, while recent advancements stem cell biology have allowed use populations to derive such models. These include three-dimensional (3D) as cell-based embryos (SCME) well organoids, many which frequently derived from embryoid bodies (EB). Not only can they recapitulate 3D form function, but developmental programs governing self-organization into more complex well. Many different organoids SCME constructs been generated years recreate tissue that give rise its cellular composition unique morphology. It is purpose this narrative literature review describe summarize recently organoid their recapitulation genetic acquired disease. Owing examined, focus on injury associated with embryonic/fetal tissues.

Язык: Английский

Multimodal characterization of murine gastruloid development DOI Creative Commons
Simon Suppinger,

Marietta Zinner,

Nadim Aizarani

и другие.

Cell stem cell, Год журнала: 2023, Номер 30(6), С. 867 - 884.e11

Опубликована: Май 19, 2023

Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development compare them with the in vivo embryo. We developed high-throughput handling imaging pipeline to spatially monitor symmetry breaking report an early spatial variability pluripotency determining binary response Wnt activation. Although gastruloid-core revert pluripotency, peripheral become primitive streak-like. These two populations subsequently break radial initiate axial elongation. By performing compound screen, perturbing thousands gastruloids, derive phenotypic landscape infer networks genetic interactions. Finally, using dual modulation, improve formation anterior existing model. This work provides understand how gastruloids develop generate complex patterns vitro.

Язык: Английский

Процитировано

45
Eomes restricts Brachyury functions at the onset of mouse gastrulation DOI Open Access
Katrin M. Schüle, Jelena Weckerle, Simone Probst

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(18), С. 1627 - 1642.e7

Опубликована: Авг. 25, 2023

Язык: Английский

Процитировано

21
Three‐dimensional stem cell models of mammalian gastrulation DOI Creative Commons
David A. Turner, Alfonso Martínez Arias

BioEssays, Год журнала: 2024, Номер 46(12)

Опубликована: Авг. 28, 2024

Abstract Gastrulation is a key milestone in the development of an organism. It period cell proliferation and coordinated cellular rearrangement, that creates outline body plan. Our current understanding mammalian gastrulation has been improved by embryo culture, but there are still many open questions difficult to address because intrauterine embryos low number specimens. In case humans, additional difficulties associated with technical ethical challenges. Over last few years, pluripotent stem models being developed have potential become useful tools understand gastrulation. Here we review these special emphasis on gastruloids provide survey methods produce them robustly, their uses, relationship embryos, prospects as well limitations.

Язык: Английский

Процитировано

8
Coordination between endoderm progression and mouse gastruloid elongation controls endodermal morphotype choice DOI

Naama Farag,

Chen Sacharen,

Lara Avni

и другие.

Developmental Cell, Год журнала: 2024, Номер 59(17), С. 2364 - 2374.e4

Опубликована: Июнь 5, 2024

Язык: Английский

Процитировано

5
Recording morphogen signals reveals origins of gastruloid symmetry breaking DOI Creative Commons
Harold M. McNamara, Sabrina C. Solley, Britt Adamson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 5, 2023

Abstract When cultured in three dimensional spheroids, mammalian stem cells can reproducibly self-organize a single anterior-posterior axis and sequentially differentiate into structures resembling the primitive streak tailbud. Whereas embryo’s body axes are instructed by spatially patterned extra-embryonic cues, it is unknown how these cell gastruloids break symmetry to define (A-P) axis. Here, we use synthetic gene circuits trace early intracellular signals predict cells’ future position gastruloid. We show that Wnt signaling evolves from homogeneous state polarized state, identify critical 6-hour time period when single-cell activity predicts cellular position, prior appearance of patterns or morphology. Single-cell RNA sequencing live-imaging reveal Wnt-high Wnt-low contribute distinct types suggest axial breaking driven sorting rearrangements involving differential adhesion. further extend our approach other canonical embryonic pathways, revealing even earlier heterogeneity TGFβ A-P modulates during period. Our study reveals sequence dynamic processes transform uniform aggregate structure demonstrates morphological emerge out movements absence exogenous patterning cues. Highlights Symmetry-breaking gastruloid protocol where high posterior domain. Synthetic record Wnt, Nodal BMP with resolution. Heterogeneity at 96 h positions types. differences influenced Nodal/BMP activity.

Язык: Английский

Процитировано

13
Signaling Centers Drive Brachyury Dynamics and Lineage Commitment in mESC Aggregates DOI Creative Commons
Alexa Rabeling, Mubeen Goolam

FASEB BioAdvances, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

ABSTRACT Stem cell‐based models of embryogenesis have exploded in popularity, resulting protocols with overlapping use some reagents and differential others. As such, the precise contributions individual signaling molecules, such as Chiron BMP4, applied to whole or part aggregates, matrices, Matrigel, development these are unknown. Furthermore, different methods, matrices has yet be directly compared under same conditions. In this paper, we used a mouse embryonic stem cell aggregate model compare BMP4 pulses (applied aggregate) centers embedded them low‐percentage Matrigel. Each factor had effects on morphology, Brachyury protein expression, lineage commitment, having pulses. pulse was shown drive neural differentiation, while resulted better recapitulation aspects anterior–posterior axis formation, polarization expression anterior posterior genes observed. This further elucidates inform decisions around experimental conditions for vitro development.

Язык: Английский

Процитировано

0
Identifying cross-lineage dependencies of cell-type-specific regulators in mouse gastruloids DOI Creative Commons
Luca Braccioli, Teun van den Brand,

Noemí Alonso Saiz

и другие.

Developmental Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Negative feedback on Retinoic Acid by Brachyury guides gastruloid symmetry-breaking DOI Creative Commons

Meagan J. Hennessy,

Timothy Fulton, David A. Turner

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 4, 2023

Abstract Establishment of the vertebrate body plan requires a combination extra-embryonic signalling to establish morphogen gradients, and an underlying self-assembly mechanism that contributes pattern regulation robustness. Gastruloids are aggregates mouse embryonic stem cells break morphological symmetry polarise Brachyury ( Bra ) expression in absence signals. However, by which breaking occurs is not yet known. During gastrulation axis elongation, retinoic acid (RA) Cyp26a1 polarised along anteroposterior axis, this critical for balancing decision self-renew or differentiate. We found symmetry-breaking gastruloids coincident with separation Aldh1a2 expression, feedback from maintaining gene gastruloid posterior region. Furthermore, we reveal short temporal window where RA can negatively influence both expression. These observations lead us suggest how initial patterning, subsequent evolving network topologies create defined boundaries permits proper axial patterning growth.

Язык: Английский

Процитировано

8
The ever-growing world of gastruloids: autogenous models of mammalian embryogenesis DOI Creative Commons
Adrienne E. Sullivan, Silvia Santos

Current Opinion in Genetics & Development, Год журнала: 2023, Номер 82, С. 102102 - 102102

Опубликована: Авг. 19, 2023

During early development, extrinsic cues prompt a collection of pluripotent cells to begin the extensive process cellular differentiation that gives rise all tissues in mammalian embryo, known as gastrulation. Advances stem cell biology have resulted generation cell-based vitro models gastrulation called gastruloids. Gastruloids and subsequent gastruloid-based are tractable, scalable more accessible than embryos. As such, they opened an unprecedented avenue for modelling self-organisation, patterning fate specification. This review focuses on discussing recent advances this rapidly moving research area, clarifying what structures model underlying signal hierarchy. We highlight exciting potential these where field might be heading.

Язык: Английский

Процитировано

6
Morphogenetic constrains in the development of gastruloids: implications for mouse gastrulation DOI Creative Commons
Ulla-Maj Fiúza, Sara Bonavia, Pau Pascual-Mas

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

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

Язык: Английский

Процитировано

2