RRC ID 55026
Author Goto T, Hara H, Sanbo M, Masaki H, Sato H, Yamaguchi T, Hochi S, Kobayashi T, Nakauchi H, Hirabayashi M.
Title Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats.
Journal Nat Commun
Abstract Regeneration of human kidneys in animal models would help combat the severe shortage of donors in transplantation therapy. Previously, we demonstrated by interspecific blastocyst complementation between mouse and rats, generation of pluripotent stem cell (PSC)-derived functional pancreas, in apancreatic Pdx1 mutant mice. We, however, were unable to obtain rat PSC-derived kidneys in anephric Sall1 mutant mice, likely due to the poor contribution of rat PSCs to the mouse metanephric mesenchyme, a nephron progenitor. Here, conversely, we show that mouse PSCs can efficiently differentiate into the metanephric mesenchyme in rat, allowing the generation of mouse PSC-derived kidney in anephric Sall1 mutant rat. Glomerular epithelium and renal tubules in the kidneys are entirely composed of mouse PSC-derived cells expressing key functional markers. Importantly, the ureter-bladder junction is normally formed. These data provide proof-of-principle for interspecific blastocyst complementation as a viable approach for kidney generation.
Volume 10(1)
Pages 451
Published 2019-2-5
DOI 10.1038/s41467-019-08394-9
PII 10.1038/s41467-019-08394-9
PMID 30723213
PMC PMC6363802
MeSH Animals Blastocyst / cytology Blastocyst / metabolism Cell Differentiation Disease Models, Animal Female Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Kidney / growth & development Kidney / metabolism Kidney Failure, Chronic / genetics Kidney Failure, Chronic / metabolism Kidney Failure, Chronic / physiopathology Kidney Failure, Chronic / therapy* Male Mesoderm / cytology Mesoderm / metabolism Mice Mice, Inbred C57BL Organogenesis Pluripotent Stem Cells / cytology Pluripotent Stem Cells / metabolism Pluripotent Stem Cells / transplantation* Rats Trans-Activators / genetics Trans-Activators / metabolism Transcription Factors / genetics Transcription Factors / metabolism* Transplantation, Homologous
IF 11.878
Times Cited 16
DNA material Rat BAC RNB1 (RDB06273) RNB1-261M04