Dekel B, Metsuyanim S, Garcia A M, Quintero C, Sanchez M J, Izraeli S
Department of Pediatrics and Laboratory of Regenerative Nephrology, Edmond and Lili Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
Leukemia. 2008 Jan;22(1):103-13. doi: 10.1038/sj.leu.2404941. Epub 2007 Sep 27.
Early in mammalian development, the stem cell leukemia (SCL/TAL1) gene and its distinct 3' enhancer (SCL 3'En) specify bipotential progenitor cells that give rise to blood and endothelium, thus termed hemangioblasts. We have previously detected a minor population of SCL (+) cells in the postnatal kidney. Here, we demonstrate that cells expressing the SCL 3'En in the adult kidney are comprised of CD45+CD31- hematopoietic cells, CD45-CD31+ endothelial cells and CD45-CD31- interstitial cells. Creation of bone marrow chimeras of SCL 3'En transgenic mice into wild-type hosts shows that all three types of SCL 3'En-expressing cells in the adult kidney can originate from the bone marrow. Ischemia/reperfusion injury to the adult kidney of SCL 3'En transgenic mice results in the intrarenal elevation of SCL and FLK1 mRNA levels and of cells expressing hem-endothelial progenitor markers (CD45, CD34, c-Kit and FLK1). Furthermore, analysis of SCL 3'En in the ischemic kidneys reveals an increase in the abundance of SCL 3'En-expressing cells, predominantly within the CD45 (+) hematopoietic fraction and to a lesser extent in the CD45 (-) fraction. Our results suggest organ-injury-induced reactivation of bone marrow-derived hemangioblasts and possible local angioblastic progenitors expressing SCL and SCL 3'En.
在哺乳动物发育早期，干细胞白血病（SCL/TAL1）基因及其独特的3'增强子（SCL 3'En）决定了产生血液和内皮细胞的双能祖细胞，即所谓的成血管细胞。我们之前在出生后的肾脏中检测到少量SCL（+）细胞。在此，我们证明成年肾脏中表达SCL 3'En的细胞由CD45+CD31-造血细胞、CD45-CD31+内皮细胞和CD45-CD31-间质细胞组成。将SCL 3'En转基因小鼠的骨髓嵌合体植入野生型宿主表明，成年肾脏中所有三种表达SCL 3'En的细胞类型都可源自骨髓。SCL 3'En转基因小鼠成年肾脏的缺血/再灌注损伤导致肾脏内SCL和FLK1 mRNA水平升高，以及表达血液-内皮祖细胞标志物（CD45、CD34、c-Kit和FLK1）的细胞增多。此外，对缺血肾脏中SCL 3'En的分析显示，表达SCL 3'En的细胞数量增加，主要在CD45（+）造血部分，在CD45（-）部分较少。我们的结果表明，器官损伤可诱导骨髓来源的成血管细胞重新激活，并可能激活表达SCL和SCL 3'En的局部血管母细胞祖细胞。
