Smad1 expands the hemangioblast population within a limited developmental window.

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.

Acetylation in hormone signaling and the cell cycle.

The last decade has seen a substantial change in thinking about the role of acetylation in regulating diverse cellular processes. The correlation between histone acetylation and gene transcription has been known for many years. The cloning and biochemical characterization of the enzymes that regulate this post-translational modification has led to an understanding of the diverse role histone acetyltransferases (HATs) play in cellular function. Histone acetylases modify histones, transcription factors, co-activators, nuclear transport proteins, structural proteins and components of the cell cycle. This review focuses on the role of histone acetylases in coordinating hormone signaling and the cell cycle. Transition through the cell cycle is regulated by a family of protein kinase holoenzymes, the cyclin-dependent kinases (Cdks) and their heterodimeric cyclin partners. Recent studies have identified important cross-talk between the cell cycle regulatory apparatus and proteins regulating histone acetylation. The evidence for a dynamic interplay between components regulating the cell cycle and acetylation of target substrates provides an important new level of complexity in the mechanisms governing hormone signaling.