Guz, Y. et al. Expression of murine STF-1, a putative insulin gene transcription factor, in cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121, 11−18

Department of Anatomy and Cell Biology, SUNY Health Science Center at Brooklyn 11203.
Development (Impact Factor: 6.46). 02/1995; 121(1):11-8.
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The XlHbox 8 homeodomain protein of Xenopus and STF-1, its mammalian homolog, are selectively expressed by beta cells of adult mouse pancreatic islets, where they are likely to regulate insulin expression. We sought to determine whether the expression of the homeobox protein/s during mouse embryonic development was specific to beta cells or, alternatively, whether XlHbox 8/STF-1 protein/s were initially expressed by multipotential precursors and only later became restricted to the insulin-containing cells. With two antibodies, we studied the localization of STF-1 during murine pancreatic development. In embryos, as in adults, STF-1 was expressed by most beta cells, by subsets of the other islet cell types and by mucosal epithelial cells of the duodenum. In addition, most epithelial cells of the pancreatic duct and exocrine cells of the pancreas transiently contained STF-1. We conclude that in mouse, STF-1 not only labels a domain of intestinal epithelial cells but also provides a spatial and temporal marker of endodermal commitment to a pancreatic and subsequently, to an endocrine beta cell fate. We propose a model of pancreatic cell development that suggests that exocrine and endocrine (alpha, beta, delta and PP) cells arise from a common precursor pool of STF-1+ cells and that progression towards a defined monospecific non-beta cell type is correlated with loss of STF-1 expression.

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Available from: Yelena Guz, Oct 04, 2015
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    • "(Ahlgren et al., 1996; Guz et al., 1995; Jennings et al., 2013; Offield et al., 1996 "
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    ABSTRACT: Inactivation of the Pancreatic and Duodenal Homeobox 1 (PDX1) gene causes pancreatic agenesis, which places PDX1 high atop the regulatory network controlling development of this indispensable organ. However, little is known about the identity of PDX1 transcriptional targets. We simulated pancreatic development by differentiating human embryonic stem cells (hESCs) into early pancreatic progenitors and subjected this cell population to PDX1 chromatin immunoprecipitation sequencing (ChIP-seq). We identified more than 350 genes bound by PDX1, whose expression was upregulated on day 17 of differentiation. This group included known PDX1 targets and many genes not previously linked to pancreatic development. ChIP-seq also revealed PDX1 occupancy at hepatic genes. We hypothesized that simultaneous PDX1-driven activation of pancreatic and repression of hepatic programs underlie early divergence between pancreas and liver. In HepG2 cells and differentiating hESCs, we found that PDX1 binds and suppresses expression of endogenous liver genes. These findings rebrand PDX1 as a context-dependent transcriptional repressor and activator within the same cell type. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Stem Cell Reports 04/2015; 122(4). DOI:10.1016/j.stemcr.2015.02.015 · 5.37 Impact Factor
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    • "Immunofluorescence analysis revealed that the ATPase subunits of Swi/Snf, Brg1 and Brm, were broadly expressed in the embryonic and adult pancreas, with no observable difference in protein level between cell types within each developmental stage (Figures S2A and S2B). Because of the unique and dynamic expression pattern of Pdx1 in the pancreas, this transcription factor would be coexpressed with Brm-and Brg1-Swi/Snf within multipotent pancreatic progenitor cells during early embryogenesis (i.e., embryonic day E12.5 [Offield et al., 1996]), and then principally in the insulin + cells of developing (E15.5, E18.5) and adult islet b cells that express relatively high levels of Pdx1 (termed Pdx1 High [Boyer et al., 2006]), and not acinar, ductal, or other islet cell types (i.e., a, ε, d, and PP) (Guz et al., 1995; Ohlsson et al., 1993). "
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    ABSTRACT: Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β cell function. However, little is known about the positive- and negative-acting coregulators recruited to mediate transcriptional control. Here, we isolated numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf core ATPase subunits, Brg1 and Brm, distinctly affected target gene expression in β cells. Furthermore, physiological and pathophysiological conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes in vivo. We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 03/2015; 55(2). DOI:10.1016/j.celrep.2015.02.054 · 8.36 Impact Factor
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    • "For this reason, we also made use of a recently derived Pdx1 CFP fluorescent reporter allele to explore the differences in gene expression between developing endocrine progenitor cells that express either high or low levels of Pdx1. It is well known that Pdx1 marks all endocrine cells (Herrera, 2000; Gu et al., 2002) and that developing β-cells, as well as a small fraction of δ-cells, express high levels of Pdx1 (Leonard et al., 1993; Ohlsson et al., 1993; Guz et al., 1995). As expected, Insm1/Pdx1-HI cells express more β-cell-specific genes, such as Ins2, Slc2a2 and Mafa. "
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