Journal ArticleDOI
Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells.
Yun Xia,Emmanuel Nivet,Ignacio Sancho-Martinez,Thomas F. Gallegos,Keiichiro Suzuki,Daiji Okamura,Min-Zu Wu,Ilir Dubova,Concepcion Rodriguez Esteban,Nuria Montserrat,Josep M. Campistol,Juan Carlos Izpisua Belmonte +11 more
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TLDR
The differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells is reported on, providing a new platform for the study of kidney diseases and lineage commitment and open new avenues for the future application of regenerative strategies in the clinic.Abstract:
Diseases affecting the kidney constitute a major health issue worldwide. Their incidence and poor prognosis affirm the urgent need for the development of new therapeutic strategies. Recently, differentiation of pluripotent cells to somatic lineages has emerged as a promising approach for disease modelling and cell transplantation. Unfortunately, differentiation of pluripotent cells into renal lineages has demonstrated limited success. Here we report on the differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells. The generated cells demonstrated rapid and specific expression of renal progenitor markers on 4-day exposure to defined media conditions. Further maturation into ureteric bud structures was accomplished on establishment of a three-dimensional culture system in which differentiated human cells assembled and integrated alongside murine cells for the formation of chimeric ureteric buds. Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic.read more
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Modeling Development and Disease with Organoids
TL;DR: 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina, and hold promise to predict drug response in a personalized fashion.
Journal ArticleDOI
Organogenesis in a dish: modeling development and disease using organoid technologies.
TL;DR: These studies illustrated two key events in structural organization during organogenesis: cell sorting out and spatially restricted lineage commitment, which are recapitulated in organoids, which self-assemble to form the cellular organization of the organ itself.
Journal ArticleDOI
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
Minoru Takasato,Minoru Takasato,Pei Xuan Er,Han Sheng Chiu,Barbara Maier,Gregory J. Baillie,Charles Ferguson,Robert G. Parton,Ernst J. Wolvetang,Matthias S Roost,Susana M. Chuva de Sousa Lopes,Melissa H. Little,Melissa H. Little,Melissa H. Little +13 more
TL;DR: The developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors is identified and kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells are generated.
Journal ArticleDOI
Generation of cerebral organoids from human pluripotent stem cells
TL;DR: A recently established protocol for generating 3D brain tissue, so-called cerebral organoids, which closely mimics the endogenous developmental program and has the potential to model later events such as neuronal maturation and survival.
Journal ArticleDOI
An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control
TL;DR: The widespread importance of Wnt signaling in driving tissue renewal has been revealed by the identification of Axin2 and Lgr5, genes expressed in cells that are responding to Wnt signals, and this crucial role in stem cell self renewal is reviewed.
References
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Keisuke Okita,Yasuko Matsumura,Yoshiko Sato,Aki Okada,Asuka Morizane,Satoshi Okamoto,Hyenjong Hong,Masato Nakagawa,Koji Tanabe,Ken-ichi Tezuka,Toshiyuki Shibata,Takahiro Kunisada,Masayo Takahashi,Jun Takahashi,Hiroh Saji,Shinya Yamanaka +15 more
TL;DR: A simple method is reported, using p53 suppression and nontransforming L-Myc, to generate human induced pluripotent stem cells (iPSCs) with episomal plasmid vectors, which may provide iPSCs suitable for autologous and allologous stem-cell therapy in the future.
Journal ArticleDOI
Self-organizing optic-cup morphogenesis in three-dimensional culture
Mototsugu Eiraku,Nozomu Takata,Hiroki Ishibashi,Masako Kawada,Eriko Sakakura,Satoru Okuda,Kiyotoshi Sekiguchi,Taiji Adachi,Yoshiki Sasai +8 more
TL;DR: The dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse embryonic stem cell aggregates is reported, demonstrating that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulation of local epithelial properties.
Journal ArticleDOI
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
Jason R. Spence,Christopher N. Mayhew,Scott A. Rankin,Matthew F. Kuhar,Jefferson E. Vallance,Kathryn Tolle,Elizabeth E. Hoskins,Vladimir V. Kalinichenko,Susanne I. Wells,Aaron M. Zorn,Noah F. Shroyer,James M. Wells +11 more
TL;DR: A robust and efficient process is established to direct the differentiation of human PSCs into intestinal tissue in vitro using a temporal series of growth factor manipulations to mimic embryonic intestinal development and indicates that human intestinal stem cells form de novo during development.
Journal ArticleDOI
Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions
Xiaojun Lian,Jianhua Zhang,Samira M. Azarin,Kexian Zhu,Laurie B. Hazeltine,Xiaoping Bao,Cheston Hsiao,Timothy J. Kamp,Sean P. Palecek +8 more
TL;DR: Functional human cardiomyocytes differentiated via these protocols may constitute a potential cell source for heart disease modeling, drug screening and cell-based therapeutic applications.
Journal ArticleDOI
Patient-specific induced pluripotent stem-cell models for long-QT syndrome.
Alessandra Moretti,Milena Bellin,Andrea Welling,Christian Jung,Jason T. Lam,Lorenz Bott-Flügel,Tatjana Dorn,Alexander Goedel,Christian Höhnke,Franz Hofmann,Melchior Seyfarth,Daniel Sinnecker,Albert Schömig,Karl-Ludwig Laugwitz +13 more
TL;DR: It was shown that myocytes derived from patients with long-QT syndrome type 1 had an increased susceptibility to catecholamine-induced tachyarrhythmia and that beta-blockade attenuated this phenotype.