Single cell transcription revealing key transcription factors in embryonic kidney development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE276813 | GEO | 2025/11/14
REPOSITORIES: GEO
Similar Datasets
Project description:Metabolic pathways driving differentiation into nephron progenitor cells (NPCs) and renal organoids from the pluripotency stage remain poorly understood. In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and further into multicellular organoids. We found activation of distinct metabolic pathways during early-stage progression from hPSCs to NPCs; however, later-stage differentiation from NPCs to organoids, and the intervening developmental stages between them, largely shared similar metabolic profiles. Among the pathways changing in early differentiation, the alanine-aspartate-glutamate and glutamine pathways were found to be significantly altered by both an enrichment and by pathway impact analysis. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, glutamine deprivation resulted in enhanced maturation, by accelerating PAX8 expression, and enriching for podocytes as detected through single cell RNA-Seq analysis. Taken together, these findings highlight a critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and renal organoids and identify a controlling metabolic pathway of early renal differentiation.
2022-06-01 | GSE128937 | GEO
Project description:Metabolic pathways driving differentiation into nephron progenitor cells (NPCs) and renal organoids from the pluripotency stage remain poorly understood. In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and further into multicellular organoids. We found activation of distinct metabolic pathways during early-stage progression from hPSCs to NPCs; however, later-stage differentiation from NPCs to organoids, and the intervening developmental stages between them, largely shared similar metabolic profiles. Among the pathways changing in early differentiation, the alanine-aspartate-glutamate and glutamine pathways were found to be significantly altered by both an enrichment and by pathway impact analysis. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, glutamine deprivation resulted in enhanced maturation, by accelerating PAX8 expression, and enriching for podocytes as detected through single cell RNA-Seq analysis. Taken together, these findings highlight a critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and renal organoids and identify a controlling metabolic pathway of early renal differentiation.
2022-06-01 | GSE128938 | GEO
Project description:Multipotent progenitor cells (MPs) have been observed in human kidneys and particularly in Bowman's capsule and proximal tubules. The kidney owns the ability to repair local damage and renal MPs may play a role in the regenerative processes. Microarray technology was applied to identify differentially expressed genes among resident MPs isolated from glomeruli and tubules of normal renal tissue, renal proximal tubular epithelial cells (RPTECs) and mesenchymal stem cells (MSCs). The results of our analysis represent a starting point for further functional studies. Experiment Overall Design: This study includes three renal tissue samples which were processed to obtain 3 glomerular progenitor populations and 3 tubular ones. Three subcoltures of MSCs and RPTECs were included as well. The differences in gene expression patterns of the 4 cell types were found out.
2009-11-09 | E-GEOD-8611 | biostudies-arrayexpress
Project description:To understand the transcription regulation of renal tubular epithelial cells under stimuli, here we investigated transcriptome, chromatin accessibility and their dynamics through RNA-seq and ATAC-seq under the three types of treatments. We identified genome-wide functional regions which coordinated transcription regulation in human renal proximal tubule epithelial cells (HK2). Our results provide a cell type-specific landscape of chromatin dynamics under stimuli and discovered an important TF in renal tubular epithelial cells that mediated genomic response to different injury stimuli.
2022-01-01 | GSE150042 | GEO
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE119426 | GEO
Project description:In this study, we systematically performed comprehensive metabolite and transcriptome profiling of human pluripotent stem cells (hPSCs) during differentiation into NPCs and later into multicellular organoids. We found activation of distinct metabolic pathways during early stage progression from hPSCs to NPCs; however, NPCs, organoids, and the intervening developmental stages between them shared similar metabolic profiles across this later stage of maturation. Importantly, the Alanine-aspartate-glutamate and glutamine pathways were significantly altered during the first stages of differentiation. Moreover, hPSCs survived glutamine deprivation during in vitro differentiation, and NPCs were successfully generated both in the absence and presence of glutamine and glutamate. Surprisingly, metabolic deprivation resulted in enhanced maturation, specifically in podocytes, as evidenced through single cell RNA-Seq analysis. These findings highlight the critical regulatory role of glutamine metabolism in the derivation of nephron progenitor cells and kidney organoids.
2025-03-20 | GSE126719 | GEO
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that progenitor cells can be cloned from mouse medulla and cortex. Clones can be grown from a single cell and indefinitely passaged. Progenitor cells derived from renal medulla can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE120049 | GEO
Project description:Obesity can initiate and accelerate the progression of kidney diseases. However, it remains unclear how obesity affects renal dysfunction. Here, we show that a newly generated podocyte-specific tubular sclerosis complex 2 (Tsc2) knockout mouse model (Tsc2∆podocyte) develops proteinuria and dies due to end-stage renal dysfunction by 10 weeks of age. Tsc2∆podocyte mice exhibit an increased glomerular size and focal segmental glomerulosclerosis, including podocyte foot process effacement, mesangial sclerosis and proteinaceous casts. Podocytes isolated from Tsc2∆podocyte mice show nuclear factor, erythroid derived 2, like 2-mediated increased oxidative stress response on microarray analysis and their autophagic activity is lowered through the mammalian target of rapamycin (mTOR)—unc-51-like kinase 1 pathway. Rapamycin attenuated podocyte dysfunction and extends survival in Tsc2∆podocyte mice. Additionally, mTOR complex 1 (mTORC1) activity is increased in podocytes of renal biopsy specimens obtained from obese patients with chronic kidney disease. Our work shows that mTORC1 hyperactivation in podocytes leads to severe renal dysfunction and that inhibition of mTORC1 activity in podocytes could be a key therapeutic target for obesity-related kidney diseases.
2020-03-21 | GSE106828 | GEO
Project description:Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography-mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.
2019-10-08 | MTBLS1093 | MetaboLights
Project description:Adult renal stem/progenitor cells (ARPCs), first identified in the BowmanM-bM-^@M-^Ys capsule, were recently identified also in the tubular compartment and it was demonstrated that renal progenitors from both locations were positive for PAX-2, CD133 and CD24 and exhibited multipotent differentiation ability. Recent studies indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of renal progenitors with that of renal proximal tubular cells (RPTECs) and of mesenchymal stem cells (MSC) and found distinct sets of miRNAs that were specifically expressed both in tubular and glomerular ARPCs. In particular, the miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX-2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX-2 depends, at least in part, on lower miR-1915 levels and showed that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, the miR-1915 and the miR-1225-5p seems to regulate important trait of ARPCs: the stemness and the repair capacity. Sixteen samples consisting of 5 glomerular and tubular ARPCs each, 3 MSCs, and 3 RPTECS.
2013-05-30 | E-GEOD-42391 | biostudies-arrayexpress