Mouse embryonic stem cells (mESC) have been used to study lineage specification in vitro, including towards a hepatocyte-like fate, and such investigations guided lineage differentiation protocols for human (h)ESC. We recently described a four-step protocol to induce hepatocyte-like cells from hESC which also induced hepatocyte-like cell differentiation of mouse induced pluripotent stem cells. ...

The divergent homeobox gene Hex exhibits three notable expression patterns during early mouse development. Initially Hex is expressed in the primitive endoderm of the implanting blastocyst but by 5.5 dpc its transcripts are present only in a small patch of visceral endoderm at the distal tip of the egg cylinder. Lineage analysis shows that these cells move unilaterally to assume an anterior pos...

We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS) methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitiv...

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit di...

The anterior visceral endoderm (AVE) plays an important role in anterior-posterior axis formation in the mouse. The AVE functions in part by expressing secreted factors that antagonize growth factor signaling in the proximal epiblast. Here we report that the Secreted frizzled-related protein 5 (Sfrp5) gene, which encodes a secreted factor that can antagonize Wnt signaling, is expressed in the A...

Abbreviations: BMSCs: Bone Marrow-derived Stem Cells; c-MYC: Myc Proto-oncogene Protein; CXCr: CXC-Chemokine Receptor; DE: Definitive Endoderm; DPP4: Dipeptidyl Peptidase 4; EB: Embryoid Body; EGF: Epidermal Growth Factor; ES: Embryonic Stem; ESCs: Embryonic Stem Cells; FACS: Fluorescence-activated Cell Sorting; FGF: Fibroblast Growth Factor; FoXa2: Forkhead Box Protein A2; GLP1: Glucagon-like ...

The formation of the head is a multistep process beginning early in embryogenesis. Transplantation, gene knock-out and gene-transfer experiments indicate the existence of a head organizer as a separate entity, which is distinct from the trunk organizer (for reviews see Bouwmeester and Leyns, 1997; Harland and Gerhart, 1997). A common vertebrate characteristic is the successive appearance and th...

OBJECTIVE In vitro production of a definitive endoderm (DE) is an important issue in stem cell-related differentiation studies and it can assist with the production of more efficient endoderm derivatives for therapeutic applications. Despite tremendous progress in DE differentiation of human embryonic stem cells (hESCs), researchers have yet to discover universal, efficient and cost-effective p...

The cellular and molecular events regulating the induction and tissue-specific differentiation of endoderm are central to our understanding of the development and function of many organ systems. To define and characterize key components in this process, we have investigated the potential of embryonic stem (ES) cells to generate endoderm following their differentiation to embryoid bodies (EBs) i...