title: An expandable, inducible hemangioblast state regulated by fibroblast growth factor.
abstract: During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that "trap" murine cells in a proliferative state and endow them with a hemangioblast potential. These "expandable" hemangioblasts (eHBs) are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dvereide@morgridge.org.
authors.forename: David T
authors.initials: DT
authors.lastname: Vereide
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Vernella
authors.initials: V
authors.lastname: Vickerman
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Swanson
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Chu
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: McIntosh
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: jthomson@morgridge.org.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D055018:Hemangioblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D016130:Immunophenotyping; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D059467:Transcriptome
chemical_list: D005346:Fibroblast Growth Factors