Generation of Hematopoietic Stem Cells from Purified Embryonic Endothelial Cells by a Simple and Efficient Strategy  

作　　者：Zhuan Li Fan Zhou Dongbo Chen Wenyan He Yanli Ni Lingfei Luo Bing Liu 

机构地区：[1]Key Laboratory of Freshwater Fish Reproduction and Development,Ministry of Education,Laboratory of Molecular Developmental Biology,School of Life Science,Southwest University [2]307-Ivy Translational Medicine Center,Laboratory of Oncology,Affiliated Hospital of Academy of Military Medical Sciences

出　　处：《Journal of Genetics and Genomics》2013年第11期557-563,共7页遗传学报（英文版）

基　　金：supported by the Chinese National Key Program on Basic Research(Nos.2011CB964800 and 2012CB966904);the National Natural Science Foundation of China(No. 30911130360)

摘　　要：Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stein cells （HSCs） are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to- hematopoietic transition （EHT）. Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DLl-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 （El0.5） Tie2~ cells remarkably. Then, the immunophenotypically defined endothelial ceils were harvested by a combination of surface markers （Flkl＋CD31 ~CD41 CD45 Ter119 ） from the caudal half of EI0.0-EI 1.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co-cultures led to long-term, high-level, multi-lineage, and multi-organ he- matopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at El0.5, and a significant increase was detected at El 1.0, which suggests a temporally specific regulation. Taken together, tbr the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research.Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stein cells （HSCs） are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to- hematopoietic transition （EHT）. Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DLl-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 （El0.5） Tie2~ cells remarkably. Then, the immunophenotypically defined endothelial ceils were harvested by a combination of surface markers （Flkl＋CD31 ~CD41 CD45 Ter119 ） from the caudal half of EI0.0-EI 1.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co-cultures led to long-term, high-level, multi-lineage, and multi-organ he- matopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at El0.5, and a significant increase was detected at El 1.0, which suggests a temporally specific regulation. Taken together, tbr the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research.

关 键 词：Hematopoietic stem cells Endothelial-to-hematopoietic transition Endothelial cells Aorta-gonad--mesonephros region 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]