1. Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary Metabolism
- Author
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Anna Abrams, Ryousuke Satou, Prasad V. G. Katakam, Jiao Liu, Courtney M Dugas, Francesca Edgington-Giordano, and Zubaida Saifudeen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cell signaling ,Time Factors ,Cellular differentiation ,030232 urology & nephrology ,Biology ,Kidney ,03 medical and health sciences ,Glycolysis Inhibition ,Mice ,0302 clinical medicine ,Internal medicine ,Up Front Matters ,Cell Self Renewal ,otorhinolaryngologic diseases ,medicine ,Animals ,Progenitor cell ,Cells, Cultured ,Progenitor ,Wnt signaling pathway ,Cell Differentiation ,General Medicine ,Nephrons ,Embryonic stem cell ,Cell biology ,stomatognathic diseases ,030104 developmental biology ,Endocrinology ,Nephrology ,Glycolysis - Abstract
Nephron progenitor cells (NPCs) show an age-dependent capacity to balance self-renewal with differentiation. Older NPCs (postnatal day 0) exit the progenitor niche at a higher rate than younger (embryonic day 13.5) NPCs do. This behavior is reflected in the transcript profiles of young and old NPCs. Bioenergetic pathways have emerged as important regulators of stem cell fate. Here, we investigated the mechanisms underlying this regulation in murine NPCs. Upon isolation and culture in NPC renewal medium, younger NPCs displayed a higher glycolysis rate than older NPCs. Inhibition of glycolysis enhanced nephrogenesis in cultured embryonic kidneys, without increasing ureteric tree branching, and promoted mesenchymal-to-epithelial transition in cultured isolated metanephric mesenchyme. Cotreatment with a canonical Wnt signaling inhibitor attenuated but did not entirely block the increase in nephrogenesis observed after glycolysis inhibition. Furthermore, inhibition of the phosphatidylinositol 3-kinase/Akt self-renewal signaling pathway or stimulation of differentiation pathways in the NPC decreased glycolytic flux. Our findings suggest that glycolysis is a pivotal, cell-intrinsic determinant of NPC fate, with a high glycolytic flux supporting self-renewal and inhibition of glycolysis stimulating differentiation.
- Published
- 2016