Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats

Teppei Goto, Hiromasa Hara, Makoto Sanbo, Hideki Masaki, Hideyuki Sato, Tomoyuki Yamaguchi, Shinichi Hochi, Toshihiro Kobayashi, Hiromitsu Nakauchi and Masumi Hirabayashi ()
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Teppei Goto: National Institute for Physiological Sciences
Hiromasa Hara: National Institute for Physiological Sciences
Makoto Sanbo: National Institute for Physiological Sciences
Hideki Masaki: The University of Tokyo
Hideyuki Sato: The University of Tokyo
Tomoyuki Yamaguchi: The University of Tokyo
Shinichi Hochi: Shinshu University
Toshihiro Kobayashi: National Institute for Physiological Sciences
Hiromitsu Nakauchi: The University of Tokyo
Masumi Hirabayashi: National Institute for Physiological Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08394-9

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