Journal article
Direct reprogramming to human nephron progenitor-like cells using inducible piggyBac transposon expression of SNAI2-EYA1-SIX1
JM Vanslambrouck, LE Woodard, N Suhaimi, FM Williams, SE Howden, SB Wilson, A Lonsdale, PX Er, J Li, J Maksimovic, A Oshlack, MH Wilson, MH Little
Kidney International | ELSEVIER SCIENCE INC | Published : 2019
Abstract
All nephrons in the mammalian kidney arise from a transient nephron progenitor population that is lost close to the time of birth. The generation of new nephron progenitors and their maintenance in culture are central to the success of kidney regenerative strategies. Using a lentiviral screening approach, we previously generated a human induced nephron progenitor-like state in vitro using a pool of six transcription factors. Here, we sought to develop a more efficient approach for direct reprogramming of human cells that could be applied in vivo. PiggyBac transposons are a non-viral integrating gene delivery system that is suitable for in vivo use and allows for simultaneous delivery of mult..
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Awarded by National Institutes of Health
Funding Acknowledgements
We acknowledge Associate Professor Jeff Holst for the provision of validated codon-optimized 2A sequences. We thank Han Chiu, Irene Ghobrial and Alex Combes for technical support. This material is the result of work supported with resources and use of facilities at the VA Tennessee Valley Healthcare system and the Molecular Cell Biology Resource Core at Vanderbilt University Medical Center. We acknowledge the Australian Cancer Research Foundation for support of the Institute for Molecular Bioscience Imaging facility. Murdoch Children's Research Institute is supported by the Victorian Government's Operational Infrastructure Support Program. This research was funded by the National Health and Medical Research Council of Australia (GNT1041275). LEW was supported by training grants from the National Institutes of Health (2T32DK060445-11), a fellowship from Dr. and Mrs. Harold Seltzman, a pilot grant from the Vanderbilt O'Brien Renal Center [P30 DK114809], and a Career Development Award from the Department of Veterans Affairs (BX002797). MHW was supported by the National Institutes of Health (DK093660), Department of Veterans Affairs (BX002190 and BX004258) and Vanderbilt Center for Kidney Disease. MHL was funded by the NHMRC as a NHMRC Senior Principal Research Fellow (APP1042093, APP1136085).