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Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [CDP & TIP]

ABSTRACT: Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [CDP & TIP]

PROVIDER: PRJNA639513 | ENA |

REPOSITORIES: ENA

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Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [CDP & TIP]

Project description:Ureteric bud (UB) is the embryonic kidney progenitor tissue that gives rise to the collecting duct and lower urinary tract. UB-like structures generated from human pluripotent stem cells by previously reported methods show limited developmental ability and limited branching. Here we report a new method to generate UB organoids that possess epithelial polarity and tubular lumen and repeat branching morphogenesis. We also succeeded in monitoring UB tip cells by utilizing the ability of tip cells to uptake very-low-density lipoprotein, cryopreserving UB progenitor cells and expanding UB tip cells that can reconstitute the organoids and differentiate into collecting duct progenitors. Moreover, we successfully reproduced some phenotypes of multicystic dysplastic kidney (MCDK) using the UB organoids. These methods will help elucidate the developmental mechanisms of UB branching and develop a selective differentiation method for collecting duct cells, contributing to the creation of disease models for congenital renal abnormalities.

2020-06-16 | GSE152470 | GEO

Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [DiI-VLDL]

2020-06-16 | GSE152471 | GEO

Expansion of human iPSC derived ureteric bud organoids with repeated branching potential

Project description:We report a new method to generate UB organoids that possess epithelial polarity and tubular lumen and repeat branching morphogenesis. We also succeeded in monitoring UB tip cells by utilizing the ability of tip cells to uptake very-low-density lipoprotein, cryopreserving UB progenitor cells and expanding UB tip cells that can reconstitute the organoids and differentiate into collecting duct progenitors. Moreover, we successfully reproduced some phenotypes of multicystic dysplastic kidney (MCDK) using the UB organoids.

2020-07-15 | GSE152685 | GEO

Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential

Project description:Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential

| PRJNA639503 | ENA

Expansion of human iPSC derived ureteric bud organoids with repeated branching potential

Project description:Expansion of human iPSC derived ureteric bud organoids with repeated branching potential

| PRJNA640126 | ENA

Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [DiI-VLDL]

Project description:Expansion of human iPSC-derived ureteric bud organoids with repeated branching potential [DiI-VLDL]

| PRJNA639512 | ENA

HNF1B controls epithelial organization and cell polarity during ureteric bud branching and collecting duct morphogenesis

Project description:Kidney development depends critically on proper ureteric bud branching giving rise to the entire collecting duct system. The transcription factor HNF1B is required for the early steps of ureteric bud branching. Yet, the molecular and cellular events regulated by HNF1B are poorly understood. We report that specific removal of Hnf1b from the ureteric bud leads to defective cell-cell contacts and apico-basal polarity during the early branching events. High resolution ex vivo imaging combined with a membranous fluorescent reporter strategy show decreased mutant cell-rearrangements during mitosis-associated cell dispersal and severe epithelial disorganisation. Molecular analysis reveals downregulation of Gdnf-Ret pathway components and suggests that HNF1B acts both upstream and downstream of Ret-signaling by directly regulating Gfrα1 and Etv5. Subsequently, Hnf1b-deletion leads to massively mispatterned ureteric tree network, defective collecting duct differentiation and disrupted tissue architecture leading to cystogenesis. Consistently, mRNA-seq analysis performed from E15.5 control and mutant kidneys shows that the most impacted genes encode intrinsic cell-membrane components with transporter activity. Our study uncovers a fundamental and recurrring role of HNF1B in epithelial organization during early ureteric bud branching and further patterning and differentiation of the collecting duct system. Article submitted to Development. Authors: Audrey Desgrange, Claire Heliot,Ilya Skovorodkin, Saad U. Akram, Janne Heikkilä, Veli-Pekka Ronkainen, Ilkka Miinalainen I., Seppo J. Vainio and Silvia Cereghini

2017-12-15 | GSE106085 | GEO

Generation of kidney ureteric bud and collecting duct organoid

Project description:A platform for generating expandable, branching and gene-editable ureteric bud organoid from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells, and its maturation into collecting duct organoid.

2021-05-11 | GSE149109 | GEO

Distal nephron plasticity allows the induction of ureteric tip and stalk for the modelling of collecting duct disease

Project description:During development, distinct progenitors contribute to the nephrons versus the ureteric epithelium of the kidney. Indeed, previous pluripotent stem cell-derived models of kidney tissue either contain nephrons or pattern specifically to the ureteric epithelium. By reanalysing the transcriptional distinction between distal nephron and ureteric epithelium in human fetal kidney, we show here that while existing nephron-containing kidney organoids contain distal nephron epithelium and no ureteric epithelium, this distal nephron segment alone displays significant in vitro plasticity and can adopt a ureteric epithelial tip identity when isolated and cultured in defined conditions. “Induced” ureteric epithelium cultures can be cryopreserved, serially passaged without loss of identity and transitioned towards a collecting duct fate. Indeed, cultures harbouring loss-of-function mutations in PKHD1 recapitulate the cystic phenotype associated with autosomal recessive polycystic kidney disease.

2021-01-15 | GSE161255 | GEO

mRNA-Seq profile of gene expression in tip and stalk compartments of ureteric epithelium in developing mouse kidney

Project description:Morphogenesis of cellecting duct system within developing mouse kidney is driven by growth at the tips of ureteric epithelium. To characterize the transcription program within the tip compartment, here we performed mRNA-Seq of tip cells (Wnt11RFP+;Hoxb7+ cells) and stalk cells (Wnt11RFP-;Hoxb7GFP+ cells) obtained from mouse embryonic kidney through FACS. We identified tip-specific genes from these data, and verified with in situ hybridization and followed up with mechanistic study for some of the intersting targets.

2017-08-15 | GSE93267 | GEO

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