Abstract
Development of the metanephric kidney is strongly dependent on complex signaling pathways and cell–cell communication between at least four major progenitor cell populations (ureteric bud, nephron, stromal, and endothelial progenitors) in the nephrogenic zone. In recent years, the improvement of human-PSC-derived kidney organoids has opened new avenues of research on kidney development, physiology, and diseases. Moreover, the kidney organoids provide a three-dimensional (3D) in vitro model for the study of cell-cell and cell-matrix interactions in the developing kidney. In vitro re-creation of a higher-order and vascularized kidney with all of its complexity is a challenging issue; however, some progress has been made in the past decade. This review focuses on major signaling pathways and transcription factors that have been identified which coordinate cell fate determination required for kidney development. We discuss how an extensive knowledge of these complex biological mechanisms translated into the dish, thus allowed the establishment of 3D human-PSC-derived kidney organoids.
Highlights
The mammalian kidney is one of the most complex organs in the body
This review focuses on major signaling pathways and transcription factors that coordinate cell fate determination of renal progenitor cells
We intend to discuss the ways in which cell communications between nephron progenitor cells (NPCs), ureteric bud progenitor cells (UBPCs), endothelial and stromal cells during organogenesis lead to a fully patterned and vascularized kidney tissue, and how a deep knowledge of these biological mechanisms translated into the dish, allowed the establishment of PSCs-derived kidney organoids
Summary
The mammalian kidney is one of the most complex organs in the body. The kidney is the major homeostatic organ necessary for pH and electrolyte regulation, and maintenance of overall fluid balance. Several transcriptional regulators such as homeobox (Hox) paralogs, LIM1 (LIM-class homeodomain1), odd skipped related 1 (OSR1), PAX2/8 (Paired box protein 2/8), and eyes absent 1 (EYA1) have been shown to play major roles in early patterning and specification of the developing kidney (Figure 1) (Bouchard et al, 2002) These events lead to the formation of multiple distinct renal progenitor populations within the nephrogenic niche. PAX2/8 can affect signaling in the developing kidney by transcriptional regulation of GATA3 (Trans-acting T-cell-specific transcription factor), LIM1 (Narlis et al, 2007; Boualia et al, 2013), RET (Bouchard et al, 2002), SALL1 (Ranghini and Dressler, 2015), SIX2, GDNF (Brophy et al, 2001), WNT4 (Torban et al, 2006), and secreted frizzled-related protein 2 (SFRP2) (Brophy et al, 2003) genes during multiple steps. Kidney organogenesis depends on cell–cell communication between these populations that lie adjacent to each other
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