Synergizing Genomic Analysis with Biological Knowledge to Identify and Validate Novel Genes in Pancreatic Development

Overview

Journal Pancreas

Specialty Gastroenterology

Date 2012 Mar 28

PMID 22450367

Citations 6

Authors

Suparna A Sarkar

Catherine E Lee

Hannah Tipney

Anis Karimpour-Fard

Jason D Dinella

Kirstine Juhl

Jay A Walters

John C Hutton

Lawrence E Hunter

Affiliations

Soon will be listed here.

Abstract

Objective: This study investigated the utility of advanced computational techniques to large-scale genome-based data to identify novel genes that govern murine pancreatic development.

Methods: An expression data set for mouse pancreatic development was complemented with high-throughput data analyzer to identify and prioritize novel genes. Quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to validate selected genes.

Results: Four new genes whose roles in the development of murine pancreas have not previously been established were identified: cystathionine β-synthase (Cbs), Meis homeobox 1, growth factor independent 1, and aldehyde dehydrogenase 18 family, member A1. Their temporal expression during development was documented. Cbs was localized in the cytoplasm of the tip cells of the epithelial chords of the undifferentiated progenitor cells at E12.5 and was coexpressed with the pancreatic and duodenal homeobox 1 and pancreas-specific transcription factor, 1a-positive cells. In the adult pancreas, Cbs was localized primarily within the acinar compartment.

Conclusions: In silico analysis of high-throughput microarray data in combination with background knowledge about genes provides an additional reliable method of identifying novel genes. To our knowledge, the expression and localization of Cbs have not been previously documented during mouse pancreatic development.

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References

Wijekoon E, Brosnan M, Brosnan J . Homocysteine metabolism in diabetes. Biochem Soc Trans. 2007; 35(Pt 5):1175-9. DOI: 10.1042/BST0351175. View

Ratnam S, Maclean K, Jacobs R, Brosnan M, Kraus J, Brosnan J . Hormonal regulation of cystathionine beta-synthase expression in liver. J Biol Chem. 2002; 277(45):42912-8. DOI: 10.1074/jbc.M206588200. View

Hick A, van Eyll J, Cordi S, Forez C, Passante L, Kohara H . Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1. BMC Dev Biol. 2009; 9:66. PMC: 2801489. DOI: 10.1186/1471-213X-9-66. View

Zhou Q, Law A, Rajagopal J, Anderson W, Gray P, Melton D . A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell. 2007; 13(1):103-14. DOI: 10.1016/j.devcel.2007.06.001. View

Kraus J . Biochemistry and molecular genetics of cystathionine beta-synthase deficiency. Eur J Pediatr. 1998; 157 Suppl 2:S50-3. DOI: 10.1007/pl00014304. View

Kutchma A, Quayum N, Jensen J . GeneSpeed: protein domain organization of the transcriptome. Nucleic Acids Res. 2006; 35(Database issue):D674-9. PMC: 1716729. DOI: 10.1093/nar/gkl990. View

Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S . Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res. 2009; 19(4):429-38. DOI: 10.1038/cr.2009.28. View

Bjerknes M, Cheng H . Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium. Dev Biol. 2010; 345(1):49-63. DOI: 10.1016/j.ydbio.2010.06.021. View

Sugiyama T, Rodriguez R, McLean G, Kim S . Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS. Proc Natl Acad Sci U S A. 2006; 104(1):175-80. PMC: 1765430. DOI: 10.1073/pnas.0609490104. View

10.

Hisa T, Spence S, Rachel R, Fujita M, Nakamura T, Ward J . Hematopoietic, angiogenic and eye defects in Meis1 mutant animals. EMBO J. 2004; 23(2):450-9. PMC: 1271748. DOI: 10.1038/sj.emboj.7600038. View

11.

Kobberup S, Schmerr M, Dang M, Nyeng P, Jensen J, MacDonald R . Conditional control of the differentiation competence of pancreatic endocrine and ductal cells by Fgf10. Mech Dev. 2009; 127(3-4):220-34. PMC: 2849919. DOI: 10.1016/j.mod.2009.11.005. View

12.

Oster A, Jensen J, Serup P, Galante P, Madsen O, Larsson L . Rat endocrine pancreatic development in relation to two homeobox gene products (Pdx-1 and Nkx 6.1). J Histochem Cytochem. 1998; 46(6):707-15. DOI: 10.1177/002215549804600602. View

13.

Kraus J . Komrower Lecture. Molecular basis of phenotype expression in homocystinuria. J Inherit Metab Dis. 1994; 17(4):383-90. DOI: 10.1007/BF00711354. View

14.

Spagnoli F . From endoderm to pancreas: a multistep journey. Cell Mol Life Sci. 2007; 64(18):2378-90. PMC: 11138409. DOI: 10.1007/s00018-007-7184-x. View

15.

Mazzarelli J, Brestelli J, Gorski R, Liu J, Manduchi E, Pinney D . EPConDB: a web resource for gene expression related to pancreatic development, beta-cell function and diabetes. Nucleic Acids Res. 2006; 35(Database issue):D751-5. PMC: 1781120. DOI: 10.1093/nar/gkl748. View

16.

Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald R, Wright C . The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet. 2002; 32(1):128-34. DOI: 10.1038/ng959. View

17.

Bicknell L, Pitt J, Aftimos S, Ramadas R, Maw M, Robertson S . A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. Eur J Hum Genet. 2008; 16(10):1176-86. DOI: 10.1038/ejhg.2008.91. View

18.

Juhl K, Sarkar S, Wong R, Jensen J, Hutton J . Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3-null mouse. Diabetes. 2008; 57(10):2755-61. PMC: 2551686. DOI: 10.2337/db07-1126. View

19.

Kaneko Y, Kimura T, Taniguchi S, Souma M, Kojima Y, Kimura Y . Glucose-induced production of hydrogen sulfide may protect the pancreatic beta-cells from apoptotic cell death by high glucose. FEBS Lett. 2008; 583(2):377-82. DOI: 10.1016/j.febslet.2008.12.026. View

20.

van der Meer L, Jansen J, van der Reijden B . Gfi1 and Gfi1b: key regulators of hematopoiesis. Leukemia. 2010; 24(11):1834-43. DOI: 10.1038/leu.2010.195. View