title: SCL/TAL1 regulates hematopoietic specification from human embryonic stem cells.
abstract: 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.
authors.affiliation: Pfizer-Universidad de Granada-Junta de Andalucia Centre for Genomics and Oncological Research (GENyO), Granada, Spain. pedro.real@genyo.es
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Real
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Ligero
authors.forename: Veronica
authors.initials: V
authors.lastname: Ayllon
authors.forename: Veronica
authors.initials: V
authors.lastname: Ramos-Mejia
authors.forename: Clara
authors.initials: C
authors.lastname: Bueno
authors.forename: Ivan
authors.initials: I
authors.lastname: Gutierrez-Aranda
authors.forename: Oscar
authors.initials: O
authors.lastname: Navarro-Montero
authors.forename: Majlinda
authors.initials: M
authors.lastname: Lako
authors.forename: Pablo
authors.initials: P
authors.lastname: Menendez
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
chemical_list: D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D017493:Leukocyte Common Antigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C067143:TAL1 protein, human