(Journal Article): Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter.
Lechner A, Leech CA, Abraham EJ, Nolan AL, Habener JF (Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, and Harvard Medical School, 55 Fruit Street-WEL320, Boston, MA 02114, USA.)
IN:
Biochem Biophys Res Commun
2002; 293(2):670-674
Impact Factor(s) of Biochem Biophys Res Commun: 2.904 (2004), 2.836 (2003), 2.935 (2002), 2.946 (2001)
ABSTRACT: The disease diabetes mellitus arises as a consequence of a failure of the beta-cells in the islets of Langerhans of the pancreas to produce insulin in the amounts required to meet the needs of the body. Whole pancreas or islet transplants in patients with severe diabetes effectively restore insulin production. A lack of availability of donor pancreata requires the development of alternative sources of islets such as the ex vivo culture and differentiation of stem/progenitor cells. Earlier we discovered multipotential progenitor cells in islets isolated from adult human pancreata that express the neural stem cell marker nestin: nestin-positive islet-derived progenitor cells (NIPs). Recently it was shown that the exclusion of the Hoechst 33342 dye, which defines the pluripotential side population (SP) of hematopoietic stem cells, is mediated by the ATP-binding cassette transporter, ABCG2. Here we report that the human islet-derived NIPs contain a substantial subpopulation of SP cells that co-express ABCG2, MDR1, and nestin. Thus NIPs may be a potential source of adult pluripotential stem/progenitor cells useful for the production of islet tissue for transplantation into diabetic subjects.
TYPE OF PUBLICATION: Original article
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(Journal Article): Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors.
Gu G, Dubauskaite J, Melton DA (Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.)
IN:
Development
2002; 129(10):2447- 2457
Impact Factor(s) of Development: 7.149 (2004), 7.663 (2003), 8.624 (2001)
ABSTRACT: The location and lineage of cells that give rise to endocrine islets during embryogenesis has not been established nor has the origin or identity of adult islet stem cells. We have employed an inducible Cre-ER(TM)-LoxP system to indelibly mark the progeny of cells expressing either Ngn3 or Pdx1 at different stages of development. The results provide direct evidence that NGN3+ cells are islet progenitors during embryogenesis and in adult mice. In addition, we find that cells expressing Pdx1 give rise to all three types of pancreatic tissue: exocrine, endocrine and duct. Furthermore, exocrine and endocrine cells are derived from Pdx1-expressing progenitors throughout embryogenesis. By contrast, the pancreatic duct arises from PDX1+ progenitors that are set aside around embryonic day 10.5 (E9.5-E11.5). These findings suggest that lineages for exocrine, endocrine islet and duct progenitors are committed at mid-gestation.
TYPE OF PUBLICATION: Original article
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