Origin of parietal podocytes in atubular glomeruli mapped by lineage tracing.
Origin of parietal podocytes in atubular glomeruli mapped by lineage tracing.
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DOI：
10.1681/asn.2013040376
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Kevin A. Schulte;Katja Berger;P. Boor;Peggy Jirak;I. Gelman;K. Arkill;C. Neal;W. Kriz;J. Floege;B. Smeets;M. Moeller
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文献类型：
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作者：
Kevin A. Schulte;Katja Berger;P. Boor;Peggy Jirak;I. Gelman;K. Arkill;C. Neal;W. Kriz;J. Floege;B. Smeets;M. Moeller
壁足细胞是完全分化的足细胞，排列在Bowman囊内，通常只发现壁上皮细胞（佩奇）。壁足细胞在整个生命过程中形成，并经常在人类活检中观察到，特别是在患病肾脏的无小管肾小球中;然而，壁足细胞的起源尚未解决。为了评估佩奇转分化为壁足细胞的能力，我们开发并表征了一种通过电凝小鼠肾皮质来产生无小管肾小球的新方法。电凝法产生多个含有佩奇的无小管肾小球以及从血管极伸出并衬有鲍曼氏囊的壁足细胞。值得注意的是，在一些佩奇中细胞死亡的诱导是明显的。相比之下，对照动物的鲍曼氏囊和电凝肾的正常肾小球很少含有足细胞。使用三重转基因小鼠（PEC-或Pod-rtTA/LC 1/R26 R）通过诱导型和不可逆遗传标记追踪佩奇和足细胞。连续冰冻切片的检查表明内脏足细胞通过血管柄迁移到Bowman囊上;没有观察到从佩奇到足细胞的直接转分化。在单侧输尿管梗阻模型和人患病肾活检中获得了类似的结果，其中没有发生指示逐渐分化的PEC或足细胞特异性抗体染色的重叠。这些结果表明，无小管肾小球的诱导导致佩奇和随后内脏足细胞迁移到鲍曼氏囊上，而不是从佩奇转分化为壁足细胞。
Parietal podocytes are fully differentiated podocytes lining Bowman's capsule where normally only parietal epithelial cells (PECs) are found. Parietal podocytes form throughout life and are regularly observed in human biopsies, particularly in atubular glomeruli of diseased kidneys; however, the origin of parietal podocytes is unresolved. To assess the capacity of PECs to transdifferentiate into parietal podocytes, we developed and characterized a novel method for creating atubular glomeruli by electrocoagulation of the renal cortex in mice. Electrocoagulation produced multiple atubular glomeruli containing PECs as well as parietal podocytes that projected from the vascular pole and lined Bowman's capsule. Notably, induction of cell death was evident in some PECs. In contrast, Bowman's capsules of control animals and normal glomeruli of electrocoagulated kidneys rarely contained podocytes. PECs and podocytes were traced by inducible and irreversible genetic tagging using triple transgenic mice (PEC- or Pod-rtTA/LC1/R26R). Examination of serial cryosections indicated that visceral podocytes migrated onto Bowman's capsule via the vascular stalk; direct transdifferentiation from PECs to podocytes was not observed. Similar results were obtained in a unilateral ureter obstruction model and in human diseased kidney biopsies, in which overlap of PEC- or podocyte-specific antibody staining indicative of gradual differentiation did not occur. These results suggest that induction of atubular glomeruli leads to ablation of PECs and subsequent migration of visceral podocytes onto Bowman's capsule, rather than transdifferentiation from PECs to parietal podocytes.