Adult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation

被引:347
作者
Yanger, Kilangsungla [1 ,2 ]
Knigin, David [4 ,5 ,6 ]
Zong, Yiwei [1 ,2 ]
Maggs, Lara [1 ,2 ]
Gu, Guoqiang [7 ]
Akiyama, Haruhiko [8 ]
Pikarsky, Eli [4 ,5 ]
Stanger, Ben Z. [1 ,2 ,3 ]
机构
[1] Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
[4] Hadassah Hebrew Univ, Dept Immunol & Canc Res, Med Ctr, IL-91120 Jerusalem, Israel
[5] Hadassah Hebrew Univ, Dept Pathol, Med Ctr, IL-91120 Jerusalem, Israel
[6] Hadassah Hebrew Univ, Dept Obstet & Gynecol, Med Ctr, IL-91120 Jerusalem, Israel
[7] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37212 USA
[8] Gifu Univ, Dept Orthoped, Gifu 5011194, Japan
基金
欧洲研究理事会;
关键词
LIVER PROGENITOR CELLS; INJURED MOUSE-LIVER; OVAL CELLS; PARTIAL-HEPATECTOMY; EPITHELIAL-CELLS; BETA-CELLS; IN-VITRO; REGENERATION; TRANSDIFFERENTIATION; PROLIFERATION;
D O I
10.1016/j.stem.2014.06.003
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The liver is thought to utilize facultative stem cells, also known as "oval cells'' or "atypical ductal cells'' (ADCs), for regeneration following various types of injury. However, this notion has been based largely on in vitro studies and transplantation models; where lineage tracing has been used, results have been conflicting and effect sizes have been small. Here, we used genetic and nucleoside analog-based tools to mark and track the origin and contribution of various cell populations to liver regeneration in vivo following several ADC-inducing insults. We report that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.
引用
收藏
页码:340 / 349
页数:10
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