Sequence analysis of the vaccinia virus strain Western Reserve genome revealed the presence of an open reading frame (ORF), SalLAR, which has the potential to encode a transmembrane glycoprotein with homology to C-type animal lectins (

During the preparation of the manuscript, an error occurred in the wording of the final sentence of the abstract. The correct sentence appears below.To our knowledge, these results demonstrate a previously unrecognized function for GATA4 as a regulator of cardiac angiogenesis through a nonhypoxic, load, and/or disease-responsive mechanism.The JCI regrets the error.

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GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human-induced pluripotent stem cells Graphical abstract Highlights d Newly accessible chromatin in definitive endoderm is enriched for GATA motifs d Definitive endoderm patterning is significantly perturbed in GATA6 À/À cells d GATA6 interacts with multiple chromatin remodeling complexes d GATA6-dependent patterning commonly precedes the onset of gene expression

HNF-4α is a transcription factor of the nuclear hormone receptor family that is expressed in the hepatic diverticulum at the onset of liver development. Mouse embryos lacking HNF-4α fail to complete gastrulation due to dysfunction of the visceral endoderm. This early embryonic lethality has so far prevented any analyses of the contribution of HNF-4α toward liver development and hepatocyte differentiation. However, we have shown that complementation ofHNF-4 α−/−embryos with a tetraploid embryo-derived wild-type visceral endoderm rescues this early developmental arrest and allowsHNF-4 α−/−embryos to proceed normally through midgestation stages of development. Examination of these rescued embryos revealed that HNF-4α was dispensable for specification and early development of the liver. However,HNF-4α−/− fetal livers failed to express a large array of genes whose expression in differentiated hepatocytes is essential for a functional hepatic parenchyma, including genes encoding several apolipoproteins, metabolic proteins, and serum factors. In addition, we have demonstrated that HNF-4α is essential for expression of the transcription factors HNF-1α and PXR within the fetal liver. We therefore conclude that HNF-4α is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function.

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We have previously shown that the transcription factor HNF4A is required for the formation of hepatic progenitor cells from endoderm that has been derived from human induced pluripotent stem cells (iPSCs). We reasoned that we could uncover regulatory pathways with new roles in hepatocyte differentiation by identifying cellular processes that regulate HNF4A. We therefore performed a screen of 1120 small molecules with well-characterized mechanisms of action to detect those that affect the abundance of HNF4A in iPSC-derived hepatic progenitor cells. This approach uncovered several small molecules that depleted HNF4A. Of those, we chose to focus on an inhibitor of heat shock protein 90 beta (HSP90β). We show that mutation of the gene encoding HSP90β represses hepatocyte differentiation during the formation of hepatocytes from iPSCs. We reveal that HSP90β, although dispensable for expression of HNF4A mRNA, directly interacts with HNF4A protein to regulate its half-life. Our results demonstrate that HSP90β has an unappreciated role in controlling hepatic progenitor cell formation and highlight the efficiency of using small-molecule screens during the differentiation of iPSCs to reveal new molecular mechanisms that control hepatocyte formation.