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Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

ABSTRACT: Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine. Gene expression profiles of development-related gene expression in kidney bud transplants and murine kidneys.

ORGANISM(S): Mus musculus

SUBMITTER: Yasuharu Ueno

PROVIDER: E-GEOD-66454 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

Project description:Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine.

2015-07-01 | GSE66454 | GEO

Sorghum axillary bud transcriptome response to leaf removal

Project description:Basal branching in grasses, or tillering, is an important trait determining both form and function of crops. While similarities exist between eudicot and grass branching programs, one notable difference is that the tiller buds of grasses are covered by the subtending leaf, whereas eudicot buds are typically unconstrained. The current study shows that contact with the leaf sheath represses sorghum bud growth by providing a mechanical signal that cues the bud to refrain from rapid growth. Leaf removal resulted in massive reprogramming of the bud transcriptome that included signatures of epigenetic modifications, and also implicated several hormones in the response. Bud abscisic acid (ABA) transiently increased, then decreased following leaf removal relative to controls, and ABA was necessary to repress bud growth in the presence of the leaf. Jasmonic acid (JA) levels and signaling increased in buds following leaf removal. Remarkably, application of JA to buds in situ promoted growth. The repression of bud growth by leaf contact shares characteristics of thigmomorphogenic responses in other systems, including the involvement of JA, though the JA effect is opposite. The repression of bud growth by leaf contact may represent a mechanism to time tillering to an appropriate developmental stage of the plant.

2019-03-05 | GSE127822 | GEO

Massive and reproducible production of liver buds entirely from human pluripotent stem cells

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

Human iPSC derived posterior gut progenitors are expandable and capable of forming gut and liver organoids

2018-01-10 | GSE108937 | GEO

Generation of the organotypic kidney by integrating pluripotent stem cell-derived renal stroma

Project description:Organs consist of not only parenchyma but also stroma, the latter of which coordinates generation of organotypic structures. Despite recent advances in organoid technology, induction of organ-specific stroma and recapitulating the complex organ configurations from pluripotent stem cells (PSCs) has remained challenging. For the kidney, the stromal progenitor coordinates differentiation of the two parenchymal progenitors: nephron progenitor and ureteric bud. By identifying the origin and dorsoventral patterning of the renal stromal progenitor, we established its induction protocol from mouse PSCs. When the three types of progenitors were differentially induced from PSCs and assembled, the all PSC-derived organoids reproduced the complex kidney structures, with multiple types of stromal cells distributed around differentiating nephrons and branching ureteric buds. Thus, integration of PSC-derived stroma into the conventional organoids enables recapitulation of organotypic architecture.

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Effects of dynamic compressive loading on MSC chondrogenesis

Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling). Free-swelling MSC-seeded constructs were cultured for 21 days in chemically defined media. Chondrogenesis was induced with TGF-beta3. Undifferentiated controls were maintained in parallel. After 21 days of chondrogenic differentiation, a subset of constructs were subjected to 21 days of dynamic compressive loading. On days 21 and 42, construct mechanical properties and biochemical content were assessed. Microarray analysis was carried out on day 3, day 21 and day 42 constructs. 6 arrays.

2010-11-01 | E-GEOD-18879 | biostudies-arrayexpress

Mus musculus

Project description:Vascularized And Complex Organ Buds From Diverse Tissues Via Mesenchymal Cell-Driven Condensation

| PRJNA277141 | ENA

Transcriptomic analysis implicates ABA signalling and carbon supply in the differential outgrowth of petunia axillary buds

Project description:Shoot branching of flowering plants exhibits phenotypic plasticity and variability. This plasticity is determined by the activity of axillary meristems, which in turn is influenced by endogenous and exogenous cues such as nutrients and light. In many species, not all buds on the main shoot develop into branches despite favorable growing conditions. In petunia, basal buds (buds 1-3) typically do not grow out to form branches, while more apical buds (buds 6 and 7) are competent to grow. The genetic regulation of buds was explored using transcriptome analyses of petunia axillary buds at different positions on the main stem. To suppress or promote bud outgrowth, we grew the plants in media with differing phosphate (P) levels. Using RNA-seq, we found many (>5000) differentially expressed genes between bud 6 or 7, and bud 2. In addition, more genes were differentially expressed when we transferred the plants from low P to high P medium, compared with shifting from high P to low P medium. Buds 6 and 7 had increased transcript abundance of cytokinin and auxin-related genes, whereas the basal non-growing buds (bud 2 and to a lesser extent bud 3) had higher expression of strigolactone, abscisic acid, and dormancy-related genes, suggesting the outgrowth of these basal buds was actively suppressed. Consistent with this, the expression of ABA associated genes decreased significantly in apical buds after stimulating growth by switching the medium from low P to high P. Furthermore, comparisons between our data and transcriptome data from other species suggest that the suppression of outgrowth of bud 2 was correlated with a limited supply of carbon to these axillary buds. Candidate genes that might repress bud outgrowth were identified by co-expression analysis.

2023-07-26 | GSE237985 | GEO

Transcriptional Profiling of the Metanephric Kidney

Project description:In this study we identify molecules with highly restricted expression patterns during the initial stages of metanephric development, when the ureteric bud has entered the metanephric mesenchyme and initiated branching morphogenesis. Using the Affymetrix Mouse Genome 430 2.0 Array, we compare gene expression patterns in ureteric bud tips, stalks and metanephric mesenchymes from mouse E12.5 embryos. To identify conserved molecular pathways, we also analyze transcriptional profiles in rat E13.5 ureteric buds and metanephric mesenchymes using the Affymetrix Rat Genome U34 Set. Taken together, these data sets help to identify conserved and highly localized transcripts in the metanephric kidney. Keywords = Mus musculus Keywords = Rattus norvegicus Keywords = metanephric mesenchyme Keywords = ureteric bud Keywords = ureteric bud tips Keywords = ureteric bud stalks Keywords = molecular screen for spatially restricted transcripts Keywords: other

2005-07-01 | GSE1983 | GEO

Gene expression in cells encapsulated within different types of alginate microcapsules

Project description:D1 multipotent mesenchymal stromal cells (D1‐MSCs,ATCC® CRL 12424TM) and genetically modified with the lentiviral vector pSIN‐EF2‐Epo‐Pur to express erythropoietin (EPO). D1‐MSCs genetically modified to release EPO were immobilized into 3D alginatepoly‐ L‐lysine‐alginate (APA) microcapsules. Since different formulations of alginate 1.5%, poly‐L‐lysine 0.05%, alginate 0.1% and washings were designed, two types of APA microcapsules were obtained: Biological microcapsules (made of Biological formulations) and Technological microcapsules (made of Technological formulations). The expression of the cells under different conditions of these two types of microcapsules have been analyzed. The present analysis proved that the mechanical properties of the matrix in which cells are enclosed influences drastically gene expression

2017-10-30 | E-MTAB-5786 | biostudies-arrayexpress

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