TY - JOUR AB - © 2016 by The American Society of Hematology. Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the 28/17/19-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/28-kb enhancer targeted TIE21/c-KIT1/CD412 endothelial cells that were enriched for hematopoieticpotential. These fractions were isolated using reporter expression and their transcriptomes profiled by RNA-seq. There was high concordance between our signatures and those from embryos with defects at corresponding stages of hematopoiesis. Of the 6 genes that were upregulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters,LRP2, amultiligandreceptor,wasthe only gene that hadnot previously been associated with hematopoiesis.WeshowthatLRP2is indeedinvolved indefinitivehematopoiesisandbydoingsovalidatetheuseof reportergene-coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions. AU - Nasrallah, R AU - Fast, EM AU - Solaimani, P AU - Knezevic, K AU - Eliades, A AU - Patel, R AU - Thambyrajah, R AU - Unnikrishnan, A AU - Thoms, J AU - Beck, D AU - Vink, CS AU - Smith, A AU - Wong, J AU - Shepherd, M AU - Kent, D AU - Roychoudhuri, R AU - Paul, F AU - Klippert, J AU - Hammes, A AU - Willnow, T AU - Göttgens, B AU - Dzierzak, E AU - Zon, LI AU - Lacaud, G AU - Kouskoff, V AU - Pimanda, JE DA - 2016/10/13 DO - 10.1182/blood-2016-02-697870 EP - 1939 JO - Blood PY - 2016/10/13 SP - 1928 TI - Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes VL - 128 Y1 - 2016/10/13 Y2 - 2024/03/29 ER -