scholarly journals Recapitulation ofin vivo gene expression during hepatic differentiation from murine embryonic stem cells

Hepatology ◽  
2005 ◽  
Vol 42 (3) ◽  
pp. 558-567 ◽  
Author(s):  
Yusuke Yamamoto ◽  
Takumi Teratani ◽  
Hanako Yamamoto ◽  
Gary Quinn ◽  
Sigenori Murata ◽  
...  
2002 ◽  
Vol 272 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Elizabeth A. Jones ◽  
David Tosh ◽  
David I. Wilson ◽  
Susan Lindsay ◽  
Lesley M. Forrester

Genetics ◽  
2021 ◽  
Author(s):  
Natalie L Rittenhouse ◽  
Zachary M Carico ◽  
Ying Frances Liu ◽  
Holden C Stefan ◽  
Nicole L Arruda ◽  
...  

Abstract Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.


2002 ◽  
Vol 103 (s47) ◽  
pp. 37P-37P
Author(s):  
Elizabeth A. Jones ◽  
David Tosh ◽  
David I. Wilson ◽  
Susan Lindsay ◽  
Lesley M. Forrester

2008 ◽  
Vol 29 (4) ◽  
pp. 195-203 ◽  
Author(s):  
Shuichi Yano ◽  
Junichiro Miake ◽  
Einosuke Mizuta ◽  
Kasumi Manabe ◽  
Udin Bahrudin ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3613-3613
Author(s):  
Claudia Lengerke ◽  
Yuan Wang ◽  
Frank Yates ◽  
Leila Maouche-Chretien ◽  
George Q. Daley

Abstract Cdx4 and cdx1, members of the caudal family of homeodomain-containing transcriptional regulators, are important for specifying the hematopoietic fate of mesoderm in the zebrafish. We have shown that the cdx4 gene plays a role in enhancing hematopoietic fate during in vitro differentiation of murine ESCs (Davidson et al., Nature 2003). Cdx4 induces hox genes, and genetic modification of mESCs with a combination of cdx4 and hoxb4 promotes long-term engraftment of ESC-derived HSCs in lethally irradiated primary and secondary mice (Wang et al, submitted). While cdx1 is known to be a direct target of signaling by the embryonic morphogens fgf, wnt3a, and retinoids, morphogens acting upstream of cdx4 have not yet been defined. Our goal is to determine optimal morphogen conditions for hematopoietic commitment from murine embryonic stem cells by evaluating activation of the cdx-hox pathway. We have developed quantitative RT-PCR assays for the cdx genes (cdx4, cdx1 and cdx2) and multiple hox genes as well as markers specific to hematopoietic stem cells and lineages. We have used these assays, together with a reporter line engineered to express GFP from the brachury locus (Fehling et al., Development 2003), to characterize the conditions for mesodermal induction and hematopoietic fate specification following addition of morphogens to differentiating cultures of ES cells under serum-free conditions. Among all morphogens tested (BMP4, activin, nodal, wnt3a, wnt5a, sonic hedgehog, indian hedgehog, retinoic acid), only BMP4 has been found to strongly induce CDX4 gene expression within the developing embryoid bodies, while addition of the BMP4 inhibitor noggin to serum suppressed CDX4 expression. Addition of BMP4 significantly increases the number of emerging CD41+ and CD45+ cells, the precursors of definitive hematopoietic stem cells. We are currently analyzing the functional changes following BMP4 exposure, and correlating hematopoietic maturation with changes in the Hox gene expression pattern. Analysis of the cdx-hox gene pathway provides a means of otpimizing induction of hematopoietic fate by application of embryonic morphogens.


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