Massive and reproducible production of liver buds entirely from human pluripotent stem cells
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ABSTRACT:
PROVIDER: PRJNA416927 | ENA |
REPOSITORIES: ENA
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Project description:Organoid technology provides a revolutionary paradigm towards therapy, yet to be applied in humans mainly because of the reproducibility and scalability challenges. Here, we overcome these limitations by evolving scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive ‘reverse’ screen experiments, we identified effective triple progenitor populations for generating liver buds in a highly reproducible manner: hepatic endoderm, endothelial and septum mesenchyme progenitors. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass-producing homogenous and miniaturized liver buds on a clinically relevant large scale (>108-cell scale). Vascularized and functional liver tissues generated entirely from iPSC significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacture platform for multi-cellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.
2017-11-03 | GSE106465 | GEO
Project description:Organoid technology provides a revolutionary paradigm towards therapy, yet to be applied in humans mainly because of the reproducibility and scalability challenges. Here, we overcome these limitations by evolving scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive ‘reverse’ screen experiments, we identified effective triple progenitor populations for generating liver buds in a highly reproducible manner: hepatic endoderm, endothelial and septum mesenchyme progenitors. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass-producing homogenous and miniaturized liver buds on a clinically relevant large scale (>108-cell scale). Vascularized and functional liver tissues generated entirely from iPSC significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacture platform for multi-cellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.
2018-01-10 | GSE108937 | GEO
Project description:Hair-bearing human skin generated entirely from pluripotent stem cells
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Project description:Transcriptional profiling of Arabidopsis buds comparing ahl16 mutants with wild type (Col-0 ecotype). Goal was to determine the differential expression genes between the buds of mutant and wild type.
2014-04-04 | GSE56497 | GEO
Project description:Tomato flowering and fruit set require an optimal temperature of 25/22 ± 2˚C (day/night). When the air temperature reaches to above the optimal range (higher than 30/26˚C; day/night), only a small number of flower buds would develop into mature flowers and produce a reduced number of pollen. This project used the iodoTMT proteomics analysis method to identify heat-induced proteomes in these tomato flower buds.
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Project description:Lonicera japonica Thunb., known as Jin Yin Hua or Japanese honeysuckle, is an herbal medicine in Asian countries. Its flowers have been used as folk medicine for clinical practice or used as food or making healthy beverage for 1500 years in China. To investigate the molecular developmental processes from L. japonica buds to flowers under UV radiation, comparative proteomics analyses of buds and flowers were performed. Fifty-four differential proteins were identified including 42 increased proteins and 12 decreased proteins. The abundance of proteins related to glycolysis, TCA/organic acid transformation, major carbohydrate metabolism, oxidative pentose phosphate, stress, secondary metabolism, hormone, and mitochondrial electron transport were increased during flower opening process under UV radiation. Six metabolites were identified and relatively quantified by LC-MS/MS in L. japonica buds and flowers. The 1,1-diphenyl-2-picrylhydrazyl assay revealed that antioxidant activity of L. japonica buds was better than that of flowers. These results suggest that UV-B radiation could induce the production of endogenous ethylene in L. japonica buds, which facilitate the buds blossom and activate the antioxidant system. Additionally, the higher content of metabolites and antioxidant capability in L. japonica buds indicates that L. japonica buds stage might be the better harvest time compared to the flower.
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Project description:Human pluripotent stem cell (hPSC)-derived retinal organoids are three-dimensional cellular aggregates that differentiate and self-organize to closely mimic the spatial and temporal patterning of the developing human retina. Retinal organoid models serve as reliable tools for studying human retinogenesis, yet limitations in the efficiency and reproducibility of current retinal organoid differentiation protocols have limited the use of these models for more high throughput applications such as disease modelling and drug screening. To address these shortcomings, the current study aimed to standardize prior differentiation protocols to yield a highly reproducible and efficient method for generating retinal organoids. Results demonstrated that through regulation of organoid size and shape using quick reaggregation methods, retinal organoids were highly reproducible compared to more traditional methods. Additionally, the timed activation of BMP signaling within developing cells generated pure populations of retinal organoids at 100% efficiency from multiple widely used cell lines, with the default forebrain fate resulting from the inhibition of BMP signaling. Furthermore, given the ability to direct retinal or forebrain fates at complete purity, mRNA-seq analyses were then utilized to identify some of the earliest transcriptional changes that occur during the specification of these two lineages from a common progenitor. These improved methods also yielded retinal organoids with expedited differentiation timelines when compared to traditional methods. Taken together, the results of this study demonstrates the development of a novel, highly reproducible and minimally variable method for generating retinal organoids suitable for analyzing the earliest stages of human retinal/forebrain cell fate specification.
2024-02-05 | GSE254830 | GEO
Project description:Transcriptional profiling of Arabidopsis buds comparing ahl16 mutants with wild type (Col-0 ecotype). Goal was to determine the differential expression genes between the buds of mutant and wild type. Biological replicates: 3 replicates of mutant buds, 3 replicates of wildtype buds.
2014-04-04 | E-GEOD-56497 | biostudies-arrayexpress
Project description:The skin is a multilayered organ, equipped with appendages (that is, follicles and glands), that is critical for regulating body temperature and the retention of bodily fluids, guarding against external stresses and mediating the sensation of touch and pain1,2. Reconstructing appendage-bearing skin in cultures and in bioengineered grafts is a biomedical challenge that has yet to be met3-9. Here we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use stepwise modulation of the transforming growth factor β (TGFβ) and fibroblast growth factor (FGF) signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During an incubation period of 4-5 months, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis and pigmented hair follicles that are equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking the neural circuitry associated with human touch. Single-cell RNA sequencing and direct comparison to fetal specimens suggest that the skin organoids are equivalent to the facial skin of human fetuses in the second trimester of development. Moreover, we show that skin organoids form planar hair-bearing skin when grafted onto nude mice. Together, our results demonstrate that nearly complete skin can self-assemble in vitro and be used to reconstitute skin in vivo. We anticipate that our skin organoids will provide a foundation for future studies of human skin development, disease modelling and reconstructive surgery.
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Project description:Efforts to unravel the mechanisms underlying taste sensation (gustation) have largely focused on rodents. The first comprehensive database of gene expression in primate (Macaca fascicularis) taste buds is presented. This database provides a foundation for further studies in diverse aspects of taste biology. A taste bud gene expression database was generated using laser capture microdissection (LCM) of tissue freeze medium OTC embedded macaque tongue tissue blocks. We collected fungiform (FG) taste buds at the front of the tongue, circumvallate (CV) taste buds at the back of the tongue, as well as non-gustatory lingual epithelium (LE). Gene expression was also analyzed in the top and bottom portions of CV taste buds collected using LCM. Samples were collected from 10 animals - 7 female, 3 male.
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