Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors

Hendry, Caroline E., Vanslambrouck, Jessica M., Ineson, Jessica, Suhaimi, Norseha, Takasato, Minoru, Rae, Fiona and Little, Melissa H. (2013) Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors. Journal of the American Society of Nephrology, 24 9: 1424-1434. doi:10.1681/ASN.2012121143

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Author Hendry, Caroline E.
Vanslambrouck, Jessica M.
Ineson, Jessica
Suhaimi, Norseha
Takasato, Minoru
Rae, Fiona
Little, Melissa H.
Title Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors
Journal name Journal of the American Society of Nephrology   Check publisher's open access policy
ISSN 1046-6673
Publication date 2013-09-01
Year available 2013
Sub-type Article (original research)
DOI 10.1681/ASN.2012121143
Open Access Status Not Open Access
Volume 24
Issue 9
Start page 1424
End page 1434
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society of Nephrology
Language eng
Formatted abstract
Direct reprogramming involves the enforced re-expression of key transcription factors to redefine a cellular state. The nephron progenitor population of the embryonic kidney gives rise to all cells within the nephron other than the collecting duct through a mesenchyme-to-epithelial transition, but this population is exhausted around the time of birth. Here, we sought to identify the conditions under which adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors. Using a combinatorial screen for lineage-instructive transcription factors, we identified a pool of six genes (SIX1, SIX2, OSR1, EYA1, HOXA11, and SNAI2) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule (HK2) cell line. Consistent with these reprogrammed cells being nephron progenitors, we observed differential contribution of the reprogrammed population into the Six2+ nephron progenitor fields of an embryonic kidney explant. Dereplication of the pool suggested that SNAI2 can suppress E-CADHERIN, presumably assisting in the epithelial-to-mesenchymal transition (EMT) required to form nephron progenitors. However, neither TGFβ-induced EMT nor SNAI2 overexpression alone was sufficient to create this phenotype, suggesting that additional factors are required. In conclusion, these results suggest that reinitiation of kidney development from a population of adult cells by generating embryonic progenitors may be feasible, opening the way for additional cellular and bioengineering approaches to renal repair and regeneration.
Keyword Urology & Nephrology
Urology & Nephrology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID P067
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 01 Nov 2013, 00:59:57 EST by Susan Allen on behalf of Institute for Molecular Bioscience