Dawn of the organoid era

Akkerman, Ninouk; Defize, L. H. K.

doi:10.1002/bies.201600244

Cited by 58 publications

(27 citation statements)

References 115 publications

(222 reference statements)

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“…Organoids can be used to model normal developmental processes (Clevers, 2016) and can be manipulated to examine the contribution of specific signaling pathways without the need to generate transgenic animals. Organoids derived from stem cells can be induced to differentiate down specific lineages by addition and/or withdrawal of specific factors often in the presence of ECM extracts (reviewed in Akkerman & Defize, 2017;Fatehullah, Tan, & Barker, 2016;Huch & Koo, 2015;Kretzschmar & Clevers, 2016).…”

Section: Background Informationmentioning

confidence: 99%

Generating Embryonic Salivary Gland Organoids

et al. 2018

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Organoids are important research tools for studying organ morphogenesis and differentiation because they recapitulate ex vivo the native 3D organization of cells that is essential for proper cell and organ function. The composition of organoids can be manipulated to incorporate specific cell types to facilitate molecular interrogation of cell-cell interactions during organoid formation. A method for generating organoids derived from both embryonic salivary gland epithelial progenitor cells and mesenchymal support cells is described. Methods for isolating enriched populations of the epithelial cells as clusters and the mesenchyme cells as single cells from mouse embryonic submandibular salivary glands are also provided. Separating the epithelial and mesenchymal cell populations allows for independent molecular manipulation of each cell type. In addition, methods for lentiviral transduction of the mesenchyme cells and quantitative image analysis of organoids are provided. The methods described here are useful for exploring mechanisms driving organ formation. C 2018 by John Wiley & Sons, Inc.Keywords: mesenchyme r organoid r proacinar r salivary

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Section: Background Informationmentioning

confidence: 99%

Generating Embryonic Salivary Gland Organoids

et al. 2018

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“…Indeed, organoids continue to attract attention as modelling tools of developmental processes, as evidenced by the rapid emergence of different organotypic systems of varying levels of functional complexity over the recent past, including eyecups (Eiraku et al, 2011), brain (Lancaster et al, 2013;Qian et al, 2016), intestines (Tsai et al, 2017), liver buds (Asai et al, 2017;Takebe et al, 2013) among others (for reviews, see Calejo, Ilmarinen, Jongprasitkul, Skottman, & Kellomäki, 2016;Akkerman & Defize, 2017;Lancaster & Knoblich, 2014). In particular, human iPSCs, which are in a development state similar to pluripotent epiblasts (Nakamura et al, 2016;O'Leary et al, 2012), are increasingly being used to model early human embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

Self‐organization of human iPS cells into trophectoderm mimicking cysts induced by adhesion restriction using microstructured mesh scaffolds

Okeyo

Tanabe

Kurosawa³

et al. 2018

Dev Growth Differ

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Cellular dynamics leading to the formation of the trophectoderm in humans remain poorly understood owing to limited accessibility to human embryos for research into early human embryogenesis. Compared to animal models, organoids formed by self-organization of stem cells in vitro may provide better insights into differentiation and complex morphogenetic processes occurring during early human embryogenesis. Here we demonstrate that modulating the cell culture microenvironment alone can trigger self-organization of human induced pluripotent stem cells (hiPSCs) to yield trophectoderm-mimicking cysts without chemical induction. To modulate the adhesion microenvironment, we used the mesh culture technique recently developed by our group, which involves culturing hiPSCs on suspended micro-structured meshes with limited surface area for cell adhesion. We show that this adhesion-restriction strategy can trigger a two-stage self-organization of hiPSCs; first into stem cell sheets, which express pluripotency signatures until around day 8-10, then into spherical cysts following differentiation and self-organization of the sheet-forming cells. Detailed morphological analysis using immunofluorescence microscopy with both confocal and two-photon microscopes revealed the anatomy of the cysts as consisting of a squamous epithelial wall richly expressing E-cadherin and CDX2. We also confirmed that the cysts exhibit a polarized morphology with basal protrusions, which show migratory behavior when anchored. Together, our results point to the formation of cysts which morphologically resemble the trophectoderm at the late-stage blastocyst. Thus, the mesh culture microenvironment can initiate self-organization of hiPSCs into trophectoderm-mimicking cysts as organoids with potential application in the study of early embryogenesis and also in drug development.

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“…Researchers have demonstrated that cells sense the ECM stiffness by mechanoreceptors such as integrins. Thus, the ECM plays a key role in the cell fate decision (Akkerman and Defize, 2017). ECM stiffness regulates differentiation into each germ layer (Zoldan et al, 2011).…”

Section: Microenvironmental Cuesmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

Rad

Aghdami

Moghadasali

2020

Front. Cell Dev. Biol.

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Development of the metanephric kidney is strongly dependent on complex signaling pathways and cell-cell communication between at least four major progenitor cell populations (ureteric bud, nephron, stromal, and endothelial progenitors) in the nephrogenic zone. In recent years, the improvement of human-PSC-derived kidney organoids has opened new avenues of research on kidney development, physiology, and diseases. Moreover, the kidney organoids provide a three-dimensional (3D) in vitro model for the study of cell-cell and cell-matrix interactions in the developing kidney. In vitro recreation of a higher-order and vascularized kidney with all of its complexity is a challenging issue; however, some progress has been made in the past decade. This review focuses on major signaling pathways and transcription factors that have been identified which coordinate cell fate determination required for kidney development. We discuss how an extensive knowledge of these complex biological mechanisms translated into the dish, thus allowed the establishment of 3D human-PSC-derived kidney organoids.

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Dawn of the organoid era

Cited by 58 publications

References 115 publications

Generating Embryonic Salivary Gland Organoids

Generating Embryonic Salivary Gland Organoids

Self‐organization of human iPS cells into trophectoderm mimicking cysts induced by adhesion restriction using microstructured mesh scaffolds

Cellular and Molecular Mechanisms of Kidney Development: From the Embryo to the Kidney Organoid

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