Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.
Identification of adult nephron progenitors capable of kidney regeneration in zebrafish.
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DOI：
10.1038/nature09669
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发表时间：
2011-02-03
期刊：
影响因子：
64.8
通讯作者：
Davidson, Alan J.
中科院分区：
文献类型：
--
作者：
Diep, Cuong Q.;Ma, Dongdong;Deo, Rahul C.;Holm, Teresa M.;Naylor, Richard W.;Arora, Natasha;Wingert, Rebecca A.;Bollig, Frank;Djordjevic, Gordana;Lichman, Benjamin;Zhu, Hao;Ikenaga, Takanori;Ono, Fumihito;Englert, Christoph;Cowan, Chad A.;Hukriede, Neil A.;Handin, Robert I.;Davidson, Alan J.
肾功能丧失是许多肾脏疾病的基础。哺乳动物可以部分修复它们的肾单位（肾脏的功能单位），但不能形成新的肾单位。相比之下，鱼类在其整个生命周期中添加肾单位，并在损伤后重新再生肾单位，这为理解哺乳动物肾脏再生如何被治疗激活提供了一个模型。在这里，我们追踪成年斑马鱼中新肾元的来源到含有肾元祖的小细胞聚集体。由10-30个细胞组成的单个聚集体移植足以移植成体并产生多个肾单位。检测自我更新的一系列移植实验表明，肾元祖细胞寿命长，具有显著的复制潜力，与干细胞活性一致。用绿色或红色荧光蛋白标记的混合肾细胞祖细胞移植可产生一些马赛克肾细胞，表明多个肾细胞祖细胞可形成单个肾细胞。与此一致的是，透明幼虫肾元形成的实时成像显示，肾原聚集体是由多个细胞合并形成的，然后分化成肾元。综上所述，这些数据表明斑马鱼肾脏可能含有自我更新的肾元干细胞/祖细胞。这些细胞的鉴定为分离或改造哺乳动物的等效细胞和开发新的肾脏再生疗法铺平了道路。
Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10–30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.
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影响因子：
64.8
作者：
GURDON, JB
通讯作者：
GURDON, JB
影响因子：
2.7
作者：
Georgas, Kylie;Rumballe, Bree;Little, Melissa H.
通讯作者：
Little, Melissa H.
影响因子：
2.7
作者：
Hartman, Heather A.;Lai, Hsiao L.;Patterson, Larry T.
通讯作者：
Patterson, Larry T.
DOI：
10.1152/ajprenal.00394.2010
发表时间：
2010-11-01
影响因子：
4.2
作者：
Zhou, Weibin;Boucher, Rudrick C.;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
4.6
作者：
Kobayashi, A;Kwan, KM;Behringer, RR
通讯作者：
Behringer, RR