Patterns of differentiation of renin lineage cells during nephrogenesis.
Patterns of differentiation of renin lineage cells during nephrogenesis.
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肾发生过程中肾素谱系细胞的分化模式。
DOI：
10.1152/ajprenal.00151.2021
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Todorov,VladimirT
中科院分区：
文献类型：
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作者：
Kessel,Friederike;Steglich,Anne;Hickmann,Linda;LiraMartinez,Ricardo;Gerlach,Michael;Sequeira-Lopez,MariaLuisaS;Gomez,RAriel;Hugo,ChristianPM;Todorov,VladimirT
在肾形成过程中，异质肾素表达细胞作为壁细胞、肾小球细胞和肾小管细胞的祖细胞，被统称为肾素谱系细胞（rlc）。在这项研究中，我们基于特定标记物量化了不同的肾血管和肾小管细胞类型，并评估了RLC群体中的增殖和新生分化。我们使用mrencrer - mt /mG小鼠的肾脏切片进行肾脏形成。在整个数字化切片上评估标记阳性。胚胎第16天，rlc出现在发育中的肾脏中，并观察rlc中所有染色标记物的表达。rlc的增殖率与非rlc的增殖率无差异。rlc主要通过新生分化（新生）扩大。源自后肾间质（肾素生成细胞、血管平滑肌细胞和系膜细胞）基质祖细胞的rlc在肾形成过程中减少。相反，收集管系统中的水通道蛋白-2阳性rlc，胚胎时期几乎完全来自输尿管芽，在产后扩大。近端小管中来自帽间质的cubilin阳性RLC分数保持不变。总之，在肾脏形成过程中，rlc在肾脏的血管和小管间室中不断被检测到。其中，各种模式的RLC分化依赖于胚胎来源的细胞被确定。肾肾素谱系细胞（rlc）的统一特征是它们起源于表达肾素的祖细胞。rlc进化为具有不同祖先结构的胚胎异质大群体。rlc也是广泛使用的肾素-血管紧张素系统阻滞剂的靶点，它可以调节rlc的表型。揭示肾脏发育过程中rlc的不同分化模式有助于理解其细胞命运在稳态挑战和抗高血压药物使用下的变化。
Developmentally heterogeneous renin-expressing cells serve as progenitors for mural, glomerular, and tubular cells during nephrogenesis and are collectively termed renin lineage cells (RLCs). In this study, we quantified different renal vascular and tubular cell types based on specific markers and assessed proliferation and de novo differentiation in the RLC population. We used kidney sections of mRenCre-mT/mG mice throughout nephrogenesis. Marker positivity was evaluated in whole digitalized sections. Atembryonic day 16, RLCs appeared in the developing kidney, and the expression of all stained markers in RLCs was observed. The proliferation rate of RLCs did not differ from the proliferation rate of non-RLCs. RLCs expanded mainly by de novo differentiation (neogenesis). Fractions of RLCs originating from the stromal progenitors of the metanephric mesenchyme (renin-producing cells, vascular smooth muscle cells, and mesangial cells) decreased during nephrogenesis. In contrast, aquaporin-2-positive RLCs in the collecting duct system, which embryonically emerges almost exclusively from the ureteric bud, expanded postpartum. The cubilin-positive RLC fraction in the proximal tubule, deriving from the cap mesenchyme, remained constant. In summary, RLCs were continuously detectable in the vascular and tubular compartments of the kidney during nephrogenesis. Therein, various patterns of RLC differentiation that depend on the embryonic origin of the cells were identified.NEW & NOTEWORTHYThe unifying feature of the renal renin lineage cells (RLCs) is their origin from renin-expressing progenitors. RLCs evolve to an embryologically heterogeneous large population in structures with different ancestry. RLCs are also targets for the widely used renin-angiotensin-system blockers, which modulate their phenotype. Unveiling the different differentiation patterns of RLCs in the developing kidney contributes to understanding changes in their cell fate in response to homeostatic challenges and the use of antihypertensive drugs.