January 2018
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11 Reads
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January 2018
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11 Reads
January 2018
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17 Reads
January 2018
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5 Reads
Table S3. Ranked Gene List from the Comparison of Fetal Signature Genes with the Expression Data from Ulcerative Colitis Patients and Normal Individuals, Related to Figure 2
December 2017
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562 Reads
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494 Citations
Cell Stem Cell
Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells. The fate change is orchestrated by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous YAP/TAZ and induce conversion of cell fate. This provides a simple model for tissue regeneration, implicating cellular reprogramming as an essential element.
October 2013
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289 Reads
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89 Citations
Stem Cell Reports
Human pluripotent stem cells (hPSCs) could provide an infinite source of clinically relevant cells with potential applications in regenerative medicine. However, hPSC lines vary in their capacity to generate specialized cells, and the development of universal protocols for the production of tissue-specific cells remains a major challenge. Here, we have addressed this limitation for the endodermal lineage by developing a defined culture system to expand and differentiate human foregut stem cells (hFSCs) derived from hPSCs. hFSCs can self-renew while maintaining their capacity to differentiate into pancreatic and hepatic cells. Furthermore, near-homogenous populations of hFSCs can be obtained from hPSC lines which are normally refractory to endodermal differentiation. Therefore, hFSCs provide a unique approach to bypass variability between pluripotent lines in order to obtain a sustainable source of multipotent endoderm stem cells for basic studies and to produce a diversity of endodermal derivatives with a clinical value.
October 2013
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233 Reads
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369 Citations
Cell Stem Cell
Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region-specific differentiation markers. This work provides insight into mechanisms underlying development of the mammalian intestine and points to future opportunities for patient-specific regeneration of the digestive tract.
August 2012
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9 Reads
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2 Citations
Cell Stem Cell
Hair follicle regeneration is controlled by an intricate relationship between epidermal stem cells and their microenvironment. A recent report in Nature by Rompolas et al. (2012) uses two-photon live imaging to interrogate the spatial organization and cellular requirements for hair follicle regeneration by epidermal stem cells and their immediate progeny.
... Accumulating evidence indicates that inflammation in the intestine leads to uncontrolled ECM remodeling and alters the mechanical properties. Yui et al. demonstrated that DSS-induced colitis leads to significant ECM remodeling in a YAP/TAZ signalingdependent manner [118]. ECM remodeling is a key feature of IBD and is associated with disease progression and inflammation. ...
December 2017
Cell Stem Cell
... The Hippo signaling pathway is essential for regulating pancreatic development, as well as β cell proliferation, differentiation and survival. Overexpression of YAP-S6A in pancreatic progenitor cells reduces the differentiation efficiency into β-like cells, but increases the number of proliferating β-like cells [26,93,[99][100][101][102]. FGF10, fibroblast growth factor 10; EGF, epidermal growth factor; TGFβ, transforming growth factor β; Inh, inhibitor; P, passage; Ha, harmine; LY, LY364947; LIF, leukemia inhibitory factor; DE, definitive endoderm; FG, foregut; PP, pancreatic progenitor; TesR1, mTESR™1; BMP4, bone morphogenetic protein 4; bFGF, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; MEF, mouse embryonic fibroblast; HGF, hepatocyte growth factor; OE, overexpression. ...
October 2013
Stem Cell Reports
... For example, researchers have demonstrated that mouse colon organoids can be effectively expanded in vitro and successfully transplanted into damaged mice 145 , where they remodel functional crypt units. Similarly, fetal progenitor-derived small intestinal organoids have exhibited the ability to integrate and function in vivo 146 . When intestinal organoids derived from PSCs were implanted under the kidney capsule of mice, they displayed good permeability and peptide uptake, highlighting their potential in treating conditions like short bowel syndrome 147 . ...
October 2013
Cell Stem Cell
... Skin is the largest organ of the human body; it plays a key role in protecting the body against pathogens. The homeostasis of skin tissue is maintained by rare but pluripotent epidermal stem cells (EpSCs) and their progeny, transient amplifying (TA) cells [1,2]. As pluripotent cells, EpSCs not only have an unlimited self-renewal capability to maintain a certain population but they also differentiate to form structures such as hair follicles and sebaceous glands [2,3]. ...
August 2012
Cell Stem Cell