Understanding axial progenitor biology in vivo and in vitro

Development, Год журнала: 2021, Номер 148(4)

Опубликована: Фев. 15, 2021

The generation of the components that make up embryonic body axis, such as spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by coordinated production various cell types from a pool posteriorly-located axial progenitors. Here, we review key features this biology progenitors, including neuromesodermal common precursors trunk musculature. We discuss recent developments vitro progenitors their potential implications disease modelling regenerative medicine.

Язык: Английский

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3D gastruloids: a novel frontier in stem cell-based in vitro modeling of mammalian gastrulation

Trends in Cell Biology, Год журнала: 2021, Номер 31(9), С. 747 - 759

Опубликована: Июль 22, 2021

3D gastruloids, aggregates of embryonic stem cells that recapitulate key aspects gastrula-stage embryos, have emerged as a powerful tool to study the early stages mammalian post-implantation development in vitro. Owing their tractable nature and relative ease by which they can be generated large numbers, gastruloids provide an unparalleled opportunity normal pathological embryogenesis from bottom-up perspective high-throughput manner. Here, we review how gastruloid models exploited deepen our understanding development. In addition, discuss current limitations, potential clinical applications, ethical implications this emerging model system.

Язык: Английский

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Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июнь 2, 2021

Abstract Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates mouse with an experimentally engineered morphogen signalling centre, functions as organizer, results the development embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses these embryoids form three germ layers through gastrulation process they exhibit wide range developmental structures, highly similar to neurula-stage embryos. Embryoids are organized around axial chordamesoderm, dorsal neural plate displays histological properties murine embryo neuroepithelium folds into tube patterned antero-posteriorly posterior midbrain tip tail. Lateral display somitic intermediate mesoderm, beating cardiac tissue anteriorly formation vasculature network. Ventrally, differentiate primitive gut tube, which is both dorso-ventrally. Altogether, provide model mammalian extensive layer derivatives promises be powerful tool for studies disease modelling.

Язык: Английский

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Axial elongation of caudalized human organoids mimics aspects of neural tube development

Development, Год журнала: 2021, Номер 148(12)

Опубликована: Июнь 15, 2021

Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects morphological temporal gene expression patterns development. Elongating organoids consist largely neuroepithelial compartments contain TBXT+SOX2+ neuro-mesodermal progenitors addition PAX6+NES+ progenitors. A critical threshold agonism stimulated singular axial extensions while maintaining multiple lineages, such displayed regionalized anterior-to-posterior HOX hindbrain (HOXB1) regions spatially distinct brachial (HOXC6) thoracic (HOXB9) regions. CRISPR interference-mediated silencing TBXT, a pathway target, increased compartmentalization, abrogated disrupted uniaxial elongation. Together, results demonstrate potent capacity hPSC undergo manner can used dissect cellular organization patterning decisions dictate early nervous system

Язык: Английский

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Human embryonic development: from peri-implantation to gastrulation

Trends in Cell Biology, Год журнала: 2021, Номер 32(1), С. 18 - 29

Опубликована: Авг. 17, 2021

Язык: Английский

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