title: Smad1 expands the hemangioblast population within a limited developmental window.
abstract: Bone morphogenetic protein (BMP) signaling is an important regulator of hematovascular development. However, the progenitor population that responds to BMP signaling is undefined, and the relative role of downstream mediators including Smad1 is unclear. We find that Smad1 shows a distinctive expression profile as embryonic stem (ES) cells undergo differentiation in the embryoid body (EB) system, with peak levels in cell populations enriched for the hemangioblast. To test the functional relevance of this observation, we generated an ES cell line that allows temporal control of ectopic Smad1 expression. Continuous expression of Smad1 from day 2 of EB culture does not disturb hematopoiesis, according to colony assays. In contrast, a pulse of Smad1 expression exclusively between day 2 and day 2.25 expands the population of progenitors for primitive erythroblasts and other hematopoietic lineages. This effect correlates with increased levels of transcripts encoding markers for the hemangioblast, including Runx1, Scl, and Gata2. Indeed, the pulse of Smad1 induction also expands the blast colony-forming cell (BL-CFC) population at a level that is fully sufficient to explain subsequent increases in hematopoiesis. Our data demonstrate that Smad1 expression is sufficient to expand the number of cells that commit to hemangioblast fate.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Chanin Rm 501, 1300 Morris Park Ave, Bronx, NY 10461, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Zafonte
authors.forename: Susanna
authors.initials: S
authors.lastname: Liu
authors.forename: Macarena
authors.initials: M
authors.lastname: Lynch-Kattman
authors.forename: Ingrid
authors.initials: I
authors.lastname: Torregroza
authors.forename: Luke
authors.initials: L
authors.lastname: Benvenuto
authors.forename: Marion
authors.initials: M
authors.lastname: Kennedy
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D051898:Smad1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
chemical_list: C497399:SMAD1 protein, human; D051898:Smad1 Protein