Chao Gao1, Lihe Chen2, Enuo Chen1, Akaki Tsilosani1, Yang Xia3, Wenzheng Zhang4. 1. Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, New York. 2. Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, Bethesda, Maryland. 3. Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, Texas. 4. Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, New York zhangw1@mail.amc.edu.
Abstract
BACKGROUND: Progenitor cells have clonogenicity, self-renewal, and multipotential capacity, and they can generate multiple types of cells during development. Evidence demonstrating the existence of such progenitor cells for renal distal segments is lacking. METHODS: To identify Aqp2+ progenitor (AP) cells, we performed in vivo lineage tracing using both constitutive (Aqp2Cre RFP/+) and Tamoxifen-inducible (Aqp2ECE/+ RFP/+, Aqp2ECE/+ Brainbow/+, and Aqp2ECE/+ Brainbow/Brainbow) mouse models. Aqp2Cre RFP/+ mice were analyzed from E14.5 to adult stage. The inducible models were induced at P1 and examined at P3 and P42, respectively. Multiple segment- or cell-specific markers were used for high-resolution immunofluorescence confocal microscopy analyses to identify the cell types derived from Aqp2+ cells. RESULTS: Both Aqp2Cre and Aqp2ECE/+ faithfully indicate the activation of the endogenous Aqp2 promoter for lineage tracing. A subset of Aqp2+ cells behaves as potential AP. Aqp2Cre-based lineage tracing revealed that embryonic APs generate five types of cells, which form the late distal convoluted tubule (DCT2), connecting tubule segments 1 and 2 (CNT1 and CNT2, respectively), and collecting ducts (CDs). The α- and β-intercalated cells were apparently derived from embryonic AP in a stepwise manner. Aqp2ECE/+ -based lineage tracing identified cells coexpressing Aqp2 and V-ATPase subunits B1 and B2 as the potential AP. Neonate APs generate daughter cells either inheriting their property (self-renewal) or evolving into various DCT2, CNT, or CD cells (multipotentiality), forming single cell-derived multiple-cell clones (clonogenicity) during development. CONCLUSION: Our study demonstrates that unique Aqp2+ B1B2+ cells are the potential APs to generate DCT2, CNT, CNT2, and CD segments.
BACKGROUND: Progenitor cells have clonogenicity, self-renewal, and multipotential capacity, and they can generate multiple types of cells during development. Evidence demonstrating the existence of such progenitor cells for renal distal segments is lacking. METHODS: To identify Aqp2+ progenitor (AP) cells, we performed in vivo lineage tracing using both constitutive (Aqp2Cre RFP/+) and Tamoxifen-inducible (Aqp2ECE/+ RFP/+, Aqp2ECE/+ Brainbow/+, and Aqp2ECE/+ Brainbow/Brainbow) mouse models. Aqp2Cre RFP/+ mice were analyzed from E14.5 to adult stage. The inducible models were induced at P1 and examined at P3 and P42, respectively. Multiple segment- or cell-specific markers were used for high-resolution immunofluorescence confocal microscopy analyses to identify the cell types derived from Aqp2+ cells. RESULTS: Both Aqp2Cre and Aqp2ECE/+ faithfully indicate the activation of the endogenous Aqp2 promoter for lineage tracing. A subset of Aqp2+ cells behaves as potential AP. Aqp2Cre-based lineage tracing revealed that embryonic APs generate five types of cells, which form the late distal convoluted tubule (DCT2), connecting tubule segments 1 and 2 (CNT1 and CNT2, respectively), and collecting ducts (CDs). The α- and β-intercalated cells were apparently derived from embryonic AP in a stepwise manner. Aqp2ECE/+ -based lineage tracing identified cells coexpressing Aqp2 and V-ATPase subunits B1 and B2 as the potential AP. Neonate APs generate daughter cells either inheriting their property (self-renewal) or evolving into various DCT2, CNT, or CD cells (multipotentiality), forming single cell-derived multiple-cell clones (clonogenicity) during development. CONCLUSION: Our study demonstrates that unique Aqp2+ B1B2+ cells are the potential APs to generate DCT2, CNT, CNT2, and CD segments.
Authors: Sandra Rodrigo Blomqvist; Hilmar Vidarsson; Sharyn Fitzgerald; Bengt R Johansson; Anna Ollerstam; Russell Brown; A Erik G Persson; G öran Bergström G; Sven Enerbäck Journal: J Clin Invest Date: 2004-06 Impact factor: 14.808
Authors: Hugo J Snippert; Laurens G van der Flier; Toshiro Sato; Johan H van Es; Maaike van den Born; Carla Kroon-Veenboer; Nick Barker; Allon M Klein; Jacco van Rheenen; Benjamin D Simons; Hans Clevers Journal: Cell Date: 2010-10-01 Impact factor: 41.582
Authors: Nick Barker; Maarten B Rookmaaker; Pekka Kujala; Annie Ng; Marc Leushacke; Hugo Snippert; Marc van de Wetering; Shawna Tan; Johan H Van Es; Meritxell Huch; Richard Poulsom; Marianne C Verhaar; Peter J Peters; Hans Clevers Journal: Cell Rep Date: 2012-09-20 Impact factor: 9.423
Authors: Linda Madisen; Theresa A Zwingman; Susan M Sunkin; Seung Wook Oh; Hatim A Zariwala; Hong Gu; Lydia L Ng; Richard D Palmiter; Michael J Hawrylycz; Allan R Jones; Ed S Lein; Hongkui Zeng Journal: Nat Neurosci Date: 2009-12-20 Impact factor: 24.884
Authors: Mary Rose Reisenauer; Marc Anderson; Le Huang; Zhijing Zhang; Qiaoling Zhou; Bruce C Kone; Andrew P Morris; Gene D Lesage; Stuart E Dryer; Wenzheng Zhang Journal: J Biol Chem Date: 2009-12-18 Impact factor: 5.157