Mechanically induced development and maturation of human intestinal organoids in vivo

Poling, Holly M.; Wu, David; Brown, Nicole; Baker, Michael; Hausfeld, Taylor A; Huynh, Nhan; Chaffron, Samuel; Dunn, James C.Y.; Hogan, Simon P.; Wells, James M.; Helmrath, Michael A.; Mahé, Maxime M.

doi:10.1038/s41551-018-0243-9

Cited by 90 publications

(91 citation statements)

References 49 publications

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“…Alterations to the HIO culture system that enable co-differentiation or co-culture of endothelium [14], neuron [17], immune or other lineages are interesting approaches to achieve a more complete model of human intestine development, and may allow enhanced maturation of cell types. Furthermore, maturation may also require perfusable vasculature [74,75], extracellular matrix alterations [10], or other mechanical inductive cues [76]. Achieving mature intestinal tissue from iPSCs in vitro remains a major challenge in the field, and continued benchmarking against multi-organ reference atlases such as the one generated here, will be required to quantify the precision of cell state specification.…”

Section: Discussionmentioning

confidence: 99%

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

Kilik

Holloway

et al. 2020

Preprint

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Human intestinal organoids (HIOs) generated from pluripotent stem cells provide extraordinary opportunities to explore development and disease. Here, we generate a single-cell transcriptome reference atlas from HIOs and from multiple developing human organs to quantify the specificity of HIO cell fate acquisition, and to explore alternative fates. We identify epithelium-mesenchyme interactions, transcriptional regulators involved in cell fate specification, and stem cell maturation features in the primary tissue that are recapitulated in HIOs. We use an HIO time course to reconstruct the molecular dynamics of intestinal stem cell emergence, as well as the specification of multiple mesenchyme subtypes. We find that the intestinal master regulator CDX2 correlates with distinct phases of epithelial and mesenchymal development, and CDX2 deletion perturbs the differentiation of both intestinal epithelium and mesenchyme. Collectively our data provides a comprehensive and quantitative assessment of HIO development, and illuminates the molecular machinery underlying endodermal and mesodermal cell fate specification.

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Section: Discussionmentioning

confidence: 99%

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

Kilik

Holloway

et al. 2020

Preprint

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“…Despite components and stiffness, the shear force of materials also affects the development of intestinal organoids (Shyer et al, ; Shyer, Huycke, Lee, Mahadevan, & Tabin, ). Recently, Poling et al () utilized a spring coated by a degradable capsule to simulate intrinsic shear stress ( Figure b ) . After spring implantation, morphology of the intestinal organoids resembled human jejunum more closely, characterized by increase of villus height, crypt depth, and smooth muscle thickness ( Figure c ) .…”

Section: Biomaterials For Intestinal Organoid Culturementioning

confidence: 99%

Biomaterials and biosensors in intestinal organoid culture, a progress review

Huang

Jiang

Ren

et al. 2020

J Biomedical Materials Res

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As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their threedimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them. K E Y W O R D Sbiosensor, intestinal stem cell, organoid, regenerative medicine, scaffold design

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“…Most of the known cues on cell physiology have been almost exclusively using static biomaterials. However, natural ECM also exhibits dynamic interactions between the ECM mechanics and cell behavior, i.e., the ECM remodeling during disease, aging, and regeneration, which exhibit sequential stiffening or softening over time and the cell niches also impart dynamic cues to regulate organ function . Thus, to probe the effects of dynamic manners on stem cell fate is becoming particularly important in cell biology and the tissue‐engineering field.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Zhang

Yang

Abali

et al. 2019

Small

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Although mechanisms of how physical forces convert into biochemical signals are increasingly understood, it is still unknown how soft cues guide cell behavior. Herein, it is shown that the commitment and differentiation of encapsulating human mesenchymal stem cell (hMSC) spheroids in thermosensitive 3D hydrogels are simply altered by interpenetrating poly(N‐isopropylacrylamide‐co‐2‐hydroxyethyl methacrylate) (NIPAM‐HEMA) nanogel to a gelatin methacryloyl (GelMA) network. This cell‐laden hydrogel provides dynamic mechanics with covalent crosslinking coordinated reversible physical networks, which can regulate hMSCs in situ by reversibly stiffening soft niches via multicyclic temperature changes from 25 to 37 °C. The spreading of hMSC spheroids in the hydrogel is strongly dependent on myosin‐dependent traction stress with dynamic mechanical stimuli through focal adhesion kinase (FAK) signaling. Notably, the dynamic microenvironment gradually influences the expression and distribution from the basal to apical side of nuclear lamin A/C and increases the Yes‐associated protein (YAP) nuclear localization with cycles, which ultimately favors hMSCs undergoing osteogenesis (but not adipogenesis) in the soft microniche. Moreover, it is demonstrated that the viscoelastic behavior of the soft microniche can be guided by temperature through a nonlinear model. These findings highlight the central roles of the dynamic relationship between the biomechanical signals and mechanosensitive transcriptional regulators in cellular mechanosensing.

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Mechanically induced development and maturation of human intestinal organoids in vivo

Cited by 90 publications

References 49 publications

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine

Biomaterials and biosensors in intestinal organoid culture, a progress review

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

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