Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney.

Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney.
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DOI:
10.1016/j.ydbio.2008.09.010
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发表时间:
2008-12-01
影响因子:
2.7
通讯作者:
McMahon, Andrew P.
McMahon, Andrew P.
中科院分区:
生物学3区
文献类型:
--
作者:
Mugford, Joshua W.;Sipilae, Petra;McMahon, Jill A.;McMahon, Andrew P.

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哺乳动物后肾源自中间中胚层。在本报告中,我们使用分子命运图谱来证明后肾肾内的大多数细胞类型均源自后肾祖细胞的 Osr1+ 群体。这些包括集合管网络的输尿管上皮、帽间质及其肾单位上皮衍生物、间质间质、脉管系统和平滑肌。时间命运图谱显示 Osr1+ 细胞命运的逐渐限制,使得在活跃肾发生开始时,Osr1 活性仅限于 Six2+ 帽间充质肾单位祖细胞。然而,Osr1+细胞的低水平标记表明,间质间充质和帽间充质祖细胞的特化发生在后肾发育开始之前的Osr1+群体内。此外,尽管 Osr1+ 祖细胞产生肾脏的大部分,但 Osr1 功能仅对肾单位祖细胞室的发育至关重要。这些研究为后肾结构的细胞起源提供了新的见解,并为 Osr1 功能仅限于建立肾单位祖细胞库的模型提供了支持。
The mammalian metanephric kidney is derived from the intermediate mesoderm. In this report, we use molecular fate mapping to demonstrate that the majority of cell types within the metanephric kidney arise from an Osr1+ population of metanephric progenitor cells. These include the ureteric epithelium of the collecting duct network, the cap mesenchyme and its nephron epithelia derivatives, the interstitial mesenchyme, vasculature and smooth muscle. Temporal fate mapping shows a progressive restriction of Osr1+ cell fates such that at the onset of active nephrogenesis, Osr1 activity is restricted to the Six2+ cap mesenchyme nephron progenitors. However, low-level labeling of Osr1+ cells suggests that the specification of interstitial mesenchyme and cap mesenchyme progenitors occurs within the Osr1+ population prior to the onset of metanephric development. Furthermore, although Osr1+ progenitors give rise to much of the kidney, Osr1 function is only essential for the development of the nephron progenitor compartment. These studies provide new insights into the cellular origins of metanephric kidney structures and lend support to a model where Osr1 function is limited to establishing the nephron progenitor pool.
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