Abstract
The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor.
Highlights
Stem cells form a fundamental basis for normal development and tissue homeostasis and for tumorigenesis
The adult mammalian kidney is mostly devoid of stem cells and is considered a non-regenerative organ, especially when regeneration is defined by the ability to generate new nephrons and regain filtration capacity [1]
It is well-established that the simultaneous activation of receptor tyrosine kinase signaling, especially downstream of the glial cell line-derived neurotrophic factor (GDNF), rearranged during transfection (RET), and fibroblast growth factor (FGF) receptor, together with inhibitory actions of bone morphogenetic protein signaling are required for ureteric bud (UB) formation and metanephric mesenchyme induction [43,58,59,60]
Summary
Stem cells form a fundamental basis for normal development and tissue homeostasis and for tumorigenesis. The embryonic kidney hosts at least three types of lineage-specific stem cells (referred to here as progenitors) that give rise to the ureter and collecting duct system, nephrons, and the connective tissue of the stroma [2,3]. Much of our basic understanding of how the kidney develops derives from the classical in vitro tissue recombination/induction experiments in different model organisms that are complemented with in vivo gene inactivation studies in mice [14,15] These experiments have demonstrated that the mammalian kidney derives from the intermediate mesoderm, which gives rise to the three spatiotemporally distinct kidneys called pro, meso-, and metanephros [15,16,17]. The stromal cells of MM differentiate into renal stroma lineages
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