RRC ID |
55026
|
著者 |
Goto T, Hara H, Sanbo M, Masaki H, Sato H, Yamaguchi T, Hochi S, Kobayashi T, Nakauchi H, Hirabayashi M.
|
タイトル |
Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats.
|
ジャーナル |
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.
|
巻・号 |
10(1)
|
ページ |
451
|
公開日 |
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
|
引用数 |
16
|
リソース情報 |
遺伝子材料 |
Rat BAC RNB1 (RDB06273) RNB1-261M04 |