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| Item Type: | Article |
|---|---|
| Title: | Identification of novel regulators of developmental hematopoiesis using endoglin regulatory elements as molecular probes |
| Creators Name: | Nasrallah, R., Fast, E.M., Solaimani, P., Knezevic, K., Eliades, A., Patel, R., Thambyrajah, R., Unnikrishnan, A., Thoms, J., Beck, D., Vink, C.S., Smith, A., Wong, J., Shepherd, M., Kent, D., Roychoudhuri, R., Paul, F., Klippert, J., Hammes, A., Willnow, T., Göttgens, B., Dzierzak, E., Zon, L.I., Lacaud, G., Kouskoff, V. and Pimanda, J.E. |
| Abstract: | 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 -8/+7/+9kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential. 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 six genes that were up-regulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters, LRP2, a multiligand receptor, was the only gene that had not previously been associated with hematopoiesis. We show that LRP2 is indeed involved in definitive hematopoiesis and by doing so validate the use of reporter gene coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions. |
| Keywords: | Cell Line, Endoglin, Endothelial Cells, Genetic Enhancer Elements, Hematopoiesis, Low Density Lipoprotein Receptor-Related Protein-2, Mammalian Embryo, Mesoderm, Molecular Probes, Mouse Embryonic Stem Cells, Animals, Mice |
| Source: | Blood |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Volume: | 128 |
| Number: | 15 |
| Page Range: | 1928-1939 |
| Date: | 13 October 2016 |
| Additional Information: | Erratum in: Blood 130(20): 2234. |
| Official Publication: | https://doi.org/10.1182/blood-2016-02-697870 |
| PubMed: | View item in PubMed |
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