SCL/TAL1 regulates hematopoietic specification from human embryonic stem cells Real Luna, Pedro José Ligero, Gertrudis Ayllon, Verónica Ramos-Mejía, Verónica Bueno, Clara Gutiérrez-Aranda, Iván Navarro-Montero, Oscar Lako, Majlinda Menéndez, Pablo This work has been funded by The Junta de Andalucía/Fondo Europeo de Desarrollo Regional (FEDER; SAS-111244 and P10-CTS-6406 to P.J.R. and P08-CTS-3678 to P.M.), The Instituto de Salud Carlos III/FEDER (PI10/00449) to P.M.; (CP09/0063) to P.J.R. and (CP07/00059 and PI11/00119) to C.B., The MICINN (PLE-2009-0111) to P.M., The Spanish Association Against Cancer/Junta Provincial de Albacete (CI110023) to P.M., and The Marie Curie IIF (PIIF-GA-2009-236430) to V.R.-M. Determining the molecular regulators/pathways responsible for the specification of human embryonic stem cells (hESCs) into hematopoietic precursors has far-reaching implications for potential cell therapies and disease modeling. Mouse models lacking SCL/TAL1 (stem cell leukemia/T-cell acute lymphocytic leukemia 1) do not survive beyond early embryogenesis because of complete absence of hematopoiesis, indicating that SCL is a master early hematopoietic regulator. SCL is commonly found rearranged in human leukemias. However, there is barely information on the role of SCL on human embryonic hematopoietic development. Differentiation and sorting assays show that endogenous SCL expression parallels hematopoietic specification of hESCs and that SCL is specifically expressed in hematoendothelial progenitors (CD45−CD31+CD34+) and, to a lesser extent, on CD45+ hematopoietic cells. Enforced expression of SCL in hESCs accelerates the emergence of hematoendothelial progenitors and robustly promotes subsequent differentiation into primitive (CD34+CD45+) and total (CD45+) blood cells with higher clonogenic potential. Short-hairpin RNA–based silencing of endogenous SCL abrogates hematopoietic specification of hESCs, confirming the early hematopoiesis-promoting effect of SCL. Unfortunately, SCL expression on its own is not sufficient to confer in vivo engraftment to hESC-derived hematopoietic cells, suggesting that additional yet undefined master regulators are required to orchestrate the stepwise hematopoietic developmental process leading to the generation of definitive in vivo functional hematopoiesis from hESCs. 2026-01-13T10:10:56Z 2026-01-13T10:10:56Z 2012-07 journal article Real, Pedro J. et al. SCL/TAL1 regulates hematopoietic specification from human embryonic stem cells. Molecular Therapy. Volume 20, Issue 7, July 2012, Pages 1443-1453. https://doi.org/10.1038/mt.2012.49 https://hdl.handle.net/10481/109603 10.1038/mt.2012.49 eng open access Elsevier