Lineage tracing evidence for in vitro dedifferentiation but rare proliferation of mouse pancreatic beta-cells.
Understanding and manipulating pancreatic beta-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human beta-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to redifferentiate into beta-cells. To directly test whether cultured beta-cells dedifferentiate, we applied genetic lineage tracing in mice. Differentiated beta-cells were heritably labeled using the Cre-lox system, and their fate in culture was followed. We provide evidence that mouse beta-cells can undergo dedifferentiation in vitro into an insulin-, pdx1-, and glut2-negative state. However, dedifferentiated beta-cells only rarely proliferate under standard culture conditions and are eventually eliminated from cultures. Thus, the predominant mesenchymal cells seen in cultures of mouse islets are not of a beta-cell origin.
Weinberg
Noa
N
Department of Cellular Biochemistry and Human Genetics, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ouziel-Yahalom
Limor
L
Knoller
Sarah
S
Efrat
Shimon
S
Dor
Yuval
Y
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D007328:Insulin; D049452:Green Fluorescent Proteins