Haploinsufficiency of Runx1 results in the acceleration of mesodermal development and hemangioblast specification upon in vitro differentiation of ES
From the Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY; Cancer Research UK, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom; and the Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, NY.j&vl, 百拇医药
The AML1 gene (recently renamed Runx1), which encodes the DNA-binding subunit of a transcription factor of the core binding factor (CBF) family, is required for the establishment of definitive hematopoiesis. We have previously demonstrated that Runx1 is expressed in yolk sac mesodermal cells prior to the establishment of the blood islands and in the embryoid body (EB)–derived blast-colony–forming cells (BL-CFCs), the in vitro equivalent of the hemangioblast. Analysis of Runx1-deficient embryonic stem (ES) cells demonstrated that this gene is essential for the generation of normal numbers of blast colonies, the progeny of the BL-CFCs. In the present study, we analyzed the potential of Runx1+/– ES cells to determine if heterozygosity at the Runx1 locus impacts early developmental events leading to the commitment of the BL-CFCs. Our results indicate that Runx1 heterozygosity leads to an acceleration of mesodermal commitment and specification to the BL-CFCs and to the hematopoietic lineages in EBs.(Georges Lacaud Valerie Kouskoff Anne Trumble Staci Schwantz and Gordon Keller)
The AML1 gene (recently renamed Runx1), which encodes the DNA-binding subunit of a transcription factor of the core binding factor (CBF) family, is required for the establishment of definitive hematopoiesis. We have previously demonstrated that Runx1 is expressed in yolk sac mesodermal cells prior to the establishment of the blood islands and in the embryoid body (EB)–derived blast-colony–forming cells (BL-CFCs), the in vitro equivalent of the hemangioblast. Analysis of Runx1-deficient embryonic stem (ES) cells demonstrated that this gene is essential for the generation of normal numbers of blast colonies, the progeny of the BL-CFCs. In the present study, we analyzed the potential of Runx1+/– ES cells to determine if heterozygosity at the Runx1 locus impacts early developmental events leading to the commitment of the BL-CFCs. Our results indicate that Runx1 heterozygosity leads to an acceleration of mesodermal commitment and specification to the BL-CFCs and to the hematopoietic lineages in EBs.(Georges Lacaud Valerie Kouskoff Anne Trumble Staci Schwantz and Gordon Keller)