Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA; Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Stem Cell Reports. 2014 Oct 14;3(4):650-62. doi: 10.1016/j.stemcr.2014.08.008. Epub 2014 Sep 18.
The mammalian kidney is a complex organ consisting of multiple cell types. We previously showed that the Six2-expressing cap mesenchyme is a multipotent self-renewing progenitor population for the main body of the nephron, the basic functional unit of the kidney. However, the cellular mechanisms establishing stromal tissues are less clear. We demonstrate that the Foxd1-expressing cortical stroma represents a distinct multipotent self-renewing progenitor population that gives rise to stromal tissues of the interstitium, mesangium, and pericytes throughout kidney organogenesis. Fate map analysis of Foxd1-expressing cells demonstrates that a small subset of these cells contributes to Six2-expressing cells at the early stage of kidney outgrowth. Thereafter, there appears to be a strict nephron and stromal lineage boundary derived from Six2-expressing and Foxd1-expressing cell types, respectively. Taken together, our observations suggest that distinct multipotent self-renewing progenitor populations coordinate cellular differentiation of the nephron epithelium and renal stroma during mammalian kidney organogenesis.
哺乳动物的肾脏是一个由多种细胞类型组成的复杂器官。我们之前曾表明，Six2 表达的帽间充质是肾单位主体的多能自我更新祖细胞群，肾单位是肾脏的基本功能单位。然而，建立基质组织的细胞机制尚不清楚。我们证明，Foxd1 表达的皮质基质代表了一个独特的多能自我更新祖细胞群，它产生间质、肾小球系膜和周细胞的基质组织，贯穿肾脏器官发生的全过程。Foxd1 表达细胞的命运图谱分析表明，这些细胞中的一小部分在肾脏生长早期有助于 Six2 表达的细胞。此后，似乎分别由 Six2 表达和 Foxd1 表达的细胞类型产生严格的肾单位和基质谱系边界。综上所述，我们的观察结果表明，在哺乳动物肾脏器官发生过程中，不同的多能自我更新祖细胞群协调肾单位上皮和肾脏基质的细胞分化。
