RRC ID 44798
Author Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, Nishinakamura R.
Title Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells.
Journal Cell Stem Cell
Abstract Recapitulating three-dimensional (3D) structures of complex organs, such as the kidney, from pluripotent stem cells (PSCs) is a major challenge. Here, we define the developmental origins of the metanephric mesenchyme (MM), which generates most kidney components. Unexpectedly, we find that posteriorly located T(+) MM precursors are developmentally distinct from Osr1(+) ureteric bud progenitors during the postgastrulation stage, and we identify phasic Wnt stimulation and stage-specific growth factor addition as molecular cues that promote their development into the MM. We then use this information to derive MM from PSCs. These progenitors reconstitute the 3D structures of the kidney in vitro, including glomeruli with podocytes and renal tubules with proximal and distal regions and clear lumina. Furthermore, the glomeruli are efficiently vascularized upon transplantation. Thus, by reevaluating the developmental origins of metanephric progenitors, we have provided key insights into kidney specification in vivo and taken important steps toward kidney organogenesis in vitro.
Volume 14(1)
Pages 53-67
Published 2014-1-2
DOI 10.1016/j.stem.2013.11.010
PII S1934-5909(13)00501-8
PMID 24332837
MeSH Animals Biomarkers / metabolism Cell Differentiation* Cells, Cultured Colony-Forming Units Assay Embryonic Stem Cells / cytology* Embryonic Stem Cells / metabolism Humans Immunoblotting Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Kidney / chemistry Kidney / cytology* Kidney / metabolism Mesoderm / cytology* Mesoderm / metabolism Nephrons / cytology* Nephrons / metabolism Organ Culture Techniques Organogenesis / physiology* Signal Transduction
IF 20.86
Times Cited 325
Human and Animal Cells 201B7(HPS0063)