한빛사 논문
Sandrine Ettou1,2,*, Youngsook L. Jung3,*, Tomoya Miyoshi4,5,6,†, Dhawal Jain3,†, Ken Hiratsuka4,5,6,7, Valerie Schumacher1,2, Mary E. Taglienti1, Ryuji Morizane4,5,6,7,8, Peter J. Park3,8,‡ and Jordan A. Kreidberg1,2,8,‡
1Department of Urology, Boston Children’s Hospital, Boston, MA 02115, USA.
2Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
3Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
4Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA.
5Renal Division, Brigham and Women’s Hospital, Boston, MA 02115, USA.
6Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
7Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
8Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
‡Corresponding author.
*These authors contributed equally to this work.
†These authors contributed equally to this work.
Abstract
In the context of human disease, the mechanisms whereby transcription factors reprogram gene expression in reparative responses to injury are not well understood. We have studied the mechanisms of transcriptional reprogramming in disease using murine kidney podocytes as a model for tissue injury. Podocytes are a crucial component of glomeruli, the filtration units of each nephron. Podocyte injury is the initial event in many processes that lead to end-stage kidney disease. Wilms tumor-1 (WT1) is a master regulator of gene expression in podocytes, binding nearly all genes known to be crucial for maintenance of the glomerular filtration barrier. Using murine models and human kidney organoids, we investigated WT1-mediated transcriptional reprogramming during the course of podocyte injury. Reprogramming the transcriptome involved highly dynamic changes in the binding of WT1 to target genes during a reparative injury response, affecting chromatin state and expression levels of target genes.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기