2153-P: PDX1- and Nkx6.1-Immunonegative ß Cells in the Developing Human Pancreas

Pancreatic endocrine and exocrine cells are of endodermal origin and differentiate during prenatal development from the epithelial cells of the primitive ducts. A specific program of transcription factor genes expression is subsequently activated and defines the fate of pancreatic progenitors. In our studies we have analyzed the distribution of two transcription factors - PDX1 and Nkx6.1 in the developing human pancreas. The study was performed on pancreatic samples from 22 fetuses (gestational age 10-40 weeks) using double and triple immunohistochemistry with antibodies to Pdx1, Nkx6.1, insulin and glucagon. In the adult human pancreas, the maintenance of β-cell identity is associated with the presence of key transcription factors (in particular Pdx1 and Nkx6.1), and changes in their expression and/or localisation have been described in the islets of type 2 diabetic individuals. In agreement with the literature, we have shown that Pdx1 and Nkx6.1 are present in the fetal pancreas already at 10th g.w. In all investigated pancreatic samples, we have observed two types of β-cells: Pdx1-positive β-cells and population of β-cells with the Pdx1-immunonegative nuclei. The results of reactions with antibodies to Nkx6.1 were similar: β-cells with both Nkx6.1 -positive and negative nuclei were detected in the human fetal pancreas. It can be suggested, that Pdx1 and Nkx6.1 are transiently expressed in the differentiating β-cells, thereafter their expression decreases and further restores in the mature β-cells. On the other hand, differentiation of some β-cells may possibly occur without Pdx1 or Nkx6.1 expression. In addition, Pdx1-positive glucagon-containing cells were observed in the developing human pancreas. Moreover, in contrast to other researchers, we found rare glucagon-containing cells with Nkx6.1-positive nuclei. This activation of Pdx1 and Nkx6.1 possibly indicates a partial transformation of α-cells toward a β-cell phenotype (and vice-versa). Disclosure A. Proshchina: None. Y. Krivova: None. L. Gurevich: None. D. Otlyga: None. S. Saveliev: None. Funding Russian Foundation for Basic Research (18-015-00147)