TY - JOUR
T1 - In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration
AU - Rinkevich, Yuval
AU - Montoro, Daniel T.
AU - Contreras-Trujillo, Humberto
AU - Harari-Steinberg, Orit
AU - Newman, Aaron M.
AU - Tsai, Jonathan M.
AU - Lim, Xinhong
AU - Van-Amerongen, Renee
AU - Bowman, Angela
AU - Januszyk, Michael
AU - Pleniceanu, Oren
AU - Nusse, Roel
AU - Longaker, Michael T.
AU - Weissman, Irving L.
AU - Dekel, Benjamin
N1 - Funding Information: We thank Adriane Mosley for assistance with animal care and parabiosis experiments and Charlene Wang for making the tetrachimeric mice. We thank Kitty Lee and the Cell Sciences Imaging Facility Fluorescent Microscopy Core at Stanford University for technical assistance with confocal microscopy. This work was supported in part by a grant from the California Institute of Regenerative Medicine (RC1 00354) and the Smith Family Trust (to I.L.W.), the Oak Foundation and the Hagey Laboratory for Pediatric Regenerative Medicine (to M.T.L.), the Israel Scientific Foundation (910-11), Israel Cancer Research Fund (PG-27013), and the Feldman Family Visiting Professorship, Stanford School of Medicine (to B.D.). Y.R. was supported by the Human Frontier Science Program Long-Term Fellowship, the Machiah Foundation Fellowship, and the Siebel foundation (1119368-104-GHBJI).
PY - 2014/5/22
Y1 - 2014/5/22
N2 - The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.
AB - The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.
UR - http://www.scopus.com/inward/record.url?scp=84901252608&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.celrep.2014.04.018
DO - https://doi.org/10.1016/j.celrep.2014.04.018
M3 - مقالة
C2 - 24835991
SN - 2211-1247
VL - 7
SP - 1270
EP - 1283
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -