C-KIT IS A MARKER OF HUMAN PANCREATIC ENDOCRINOCYTE STEM CELLS



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The aim of our study was to analyze the expression of one of the markers of progenitor cell of different cell types - CD 117 (C-kit) - in human pancreas during prenatal development. The pancreas of human embryos and fetuses at 4-28 weeks of gestation as well as of infants aged up to 2nd postnatal month, was studied. In histological sections, the immunocytochemical reactions were performed with the antibodies against C-kit, insulin and glucagon. In situ hybridization was used for detection of proinsulin mRNA. First cells expressing C-kit were found in human pancreas at 8.5 weeks of gestation among ductal epithelial cells. At 11.5 weeks of gestation these cells were found to segregate from the ductal epithelium and start to form islets. From 8.5 weeks of gestation C-kit positive cells started to express glucagon and proinsulin mRNA, and after 11.5 weeks they also expressed insulin. Islet C-kit positive cells coexpressing both glucagon and insulin, were also found after the birth. It may be concluded that C-kit positive endocrinocyte progenitor cells are common for pancreatic islet A- and B-cells and they are preserved in he islets after the birth.

References

  1. Алеева Г.Н., Киясов А.П., Миннебаев М.М. и др. Динамика В-иА-клеточной популяций поджелудочной железы и содержания глюкозы в крови крыс при аллоксановом диабете. Бюл. экспер. биол., 2002, т. 133, № 2, с. 151-153.
  2. Blume-Jensen P., Claesson-Welsh L., Siegbahn A. et al. Activation of the human c-kit product by ligand-induced dimerization mediates circular actin reorganization and chemotaxis. EMBO J., 1991, v. 10, p. 4121-4128.
  3. Chabot B., Stephenson D.A., Chapman V.M. et al. The protooncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature, 1988, v. 335, p. 88-89.
  4. d'Auriol L., Mattei M.G., Andre C. and Galibert F. Localization of the human c-kit protooncogene on the q11-q12 region of chromosome 4. J. Hum. Genetics, 1987, v. 78, p. 374-376.
  5. Herrera P.L., Huarte J., Zufferey R. et al. Ablation of islet endocrine cells by targeted expression of hormone-promoterdriven toxigenes. Proc. Natl. Acad. Sci. USA, 1994, v. 91, p. 12999-13003.
  6. Jensen J., Heller R. S., Funder-Nielsen T. et al. Independent development of pancreatic α- and β-cells from neurogenin3expressing precursors a role for the notch pathway in repression of premature differentiation. J. Diabetes, 2000, v. 49, p. 163-176.
  7. LeBras S., Czernichow P. and Scharfmann R. A search for tyrosine kinase receptors expressed in the rat embryonic pancreas. J. Diabetol., 1998, v. 41, p. 1474-1481.
  8. Leonard J., Peers B., Johnson T. et al. Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells. Mol. Endocrinol., 1993, v. 7, p. 1275-1283.
  9. Li J., Goodyer C.G., Fellows F. and Wang R. Stem cell factor/c-Kit interactions regulate human islet-epithelial cluster proliferation and differentiation. Int. J. Biochem. Cell Biol., 2006, v. 38, p. 961-972.
  10. Li J., Quirt J., Do H.Q. et al. Expression of c-Kit receptor tyrosine kinase and effect on beta-cell development in the human fetal pancreas. Am. J. Physiol. Endocrinol. Metab., 2007, v. 293, p. 475-483.
  11. Linnekin D. Early signaling pathways activated by c-Kit in hematopoietic cells. Int. J. Biochem. Cell Biol., 1999, v. 31, p. 1053-1074.
  12. Oberg-Welsh C., Waltenberger J., Claesson-Welsh L. and Welsh M. Expression of protein tyrosine kinases in islet cells: possible role of the Flk-1 receptor for β-cell maturation from duct cells. J. Growth Factors, 1994, v. 10, p. 115-126.
  13. Ohlsson H. and Edlund T. Sequence-specific interactions of nuclear factors with the insulin gene cnhancer. J.Cell, 1986, v. 45, p. 35-44.
  14. Philo J. S., Wen J., Wypych J. et al. Human stem cell factor dimer forms a complex with two molecules of the extracellular domain of its receptor Kit. J. Biol. Chem., 1996, v. 271, p. 6895-6902.
  15. Ramiya V.K., Maraist M., Arfors K.E. et al. Reversal of insulindependent diabetes using islets generated in vitro from pancreatic stem cells. J. Nat. Med., 2000, v. 6, p. 278-282.
  16. Suzuki A., Nakauchi H. and Taniguchi H. Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. J. Diabetes, 2004, v. 53, p. 2143-2152.
  17. Welsh M., Anneren C., Lindholm C. et al. Role of tyrosine kinase signaling for beta-cell replication and survival. Ups. J. Med. Sci., 2000, v. 105, p. 7-15.
  18. Yashpal N.K., Li J. and Wang R. Characterization of c-Kit and nestin expression during islet cell development in the prenatal and postnatal rat pancreas. J. Dev. Dyn, 2004, v. 229, p. 813- 825.
  19. Zulewski H., Abraham E.J., Gerlach M.J. et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes. J. Diabetes, 2001, v. 50, p. 521-533.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2011 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: № 0110212 от 08.02.1993.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies