Year: 2018
Type: editorial
Abstract: The kidney is formed during development by reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM), which promote the induction of nephron patterning and differentiation.Traditionally, UB and MM cells including nephron progenitor cells (NPCs) have been very difficult to isolate and maintain in culture due to their propensity to differentiate when outside their developmental niche.Remarkably, in recent years researchers have succeeded in prolonging the lifespan of mouse [1], rat [1], and human [2] NPCs in vitro, offering an avenue to expand the current knowledge of mammalian kidney development, and eventually for disease modelling and drug screening studies.Alternatively, renal progenitors have also been generated from human pluripotent stem cells (hPSCs) by mimicking early kidney developmental signals in vitro.Recently, different laboratories have been able to partially reproduce kidney organogenesis in a dish using hPSCs, successfully generating so-called kidney organoids [3,4,5,6].Kidney organoids contain self-organized nephron-like structures composed of early podocyte cell clusters connected to tubular structures expressing markers of proximal tubules, loops of Henle and distal tubules [3,4,5,6].In addition, kidney organoids display proximal tubular functionality in vitro, showing selective endocytosis of dextran cargoes [5,6], as well as responding to nephrotoxic agents [4,5,6].Recent advances in the generation of kidney organoids in vitro together with state-of-art genome editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9), represent a unique opportunity to study human kidney development and disease.Congenital kidney disorders can be modelled by introducing disease mutations in hPSCs and subsequently studying the disease phenotype in differentiated kidney organoids.Following this approach, Freedman and colleagues have recently reported an in vitro human model for polycystic kidney disease (PKD) by producing hPSCs with targeted biallelic mutations in the PKD1 and PKD2 genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively.CRISPR-mutant PKD and PKD2 knockout kidney organoids formed cysts in kidney tubules, recapitulating some characteristic features of this life-threatening renal disease in vitro [6].In the same work, the authors also tested the function of hPSC lines that were gene edited so that they lacked the podocalyxin (PODXL) gene.
Source: Oncotarget
Institution: Salk Institute for Biological Studies
Language: English
Topic: Renal and related cancers
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2791066761