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The CD34 surface antigen is restricted to glucagon-expressing cells in the early developing bovine pancreas

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Abstract

Controversy remains regarding the origin of the pancreatic endocrine cells. It is generally accepted that the majority of insulin-secreting cells derive from the endodermal epithelium of the gastrointestinal tract. The aim of this study was to determine the contribution made by a particular cluster of differentiation (CD)-positive cells to the development of the bovine endocrine pancreas. In bovine embryos and foetuses with crown to rump lengths (CRL) ranging from 1 to 47 cm, cells staining positively for CD34 and/or CD133 were always more numerous in the left lobe and body of pancreas than in the right lobe. In the early stages of pancreatic development (CRL <5 cm), CD34 and/or CD133-reactive cells were concentrated within the epithelial cell cords that form the primitive pancreas. In later developmental stages (CRL >5 cm), individual or groups of CD34 and/or CD133-reactive cells were present in newly formed acini, which bulged out from the duct system that had arisen from the cords. Some of the positively stained cells accumulated in focal areas associated with hyperplastic intra-acinar cells. These “acino-insula-like complexes” appeared to enlarge with age and develop into intralobular Islets of Langerhans. Most of the described CD34 and/or CD133-reactive cells displayed co-localisation with glucagon. A negligible number of these cells showed co-localisation with insulin. Glucagon-stained cells were distinct from insulin-stained cells and were more abundant in embryonic and early foetal pancreata. Our data demonstrate that CD34 and/or CD133-reactive cells contribute to the pancreatic alpha cell population during early foetal development in cattle.

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Acknowledgments

We are grateful to Angela Ehrlich for all her drives to the abattoir in Altenburg, Germany and to Dr. G. Domel and the meat hygiene and inspection team for all the support on the ground. We greatly appreciate Dr. Joel F Habener for his kind gift of anti-Pdx1 antibody Hm253. We thank our colleagues for their insightful discussions, comments and technical help; in particular, we thank Sonja Kallendrusch for her great help in the experimental verification of our results by triple labelling. The Helsinki Group was supported by grants from the Academy of Finland (122540/2007) and The Research Funds of The University of Helsinki (914/51/2006). Paul Lochhead is funded by a fellowship from the Chief Scientist Office of the Scottish Government.

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Authors and Affiliations

  1. Institute of Anatomy, University of Leipzig, Liebigstraße 13, 04103, Leipzig, Germany

    Claudia Merkwitz & Albert M. Ricken

  2. Department of Veterinary Biosciences, University of Helsinki, P.O. Box 66, 00014, Helsinki, Finland

    Tiina Pessa-Morikawa & Antti Iivanainen

  3. Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen Foresterhill, Aberdeen, AB25 2ZD, UK

    Paul Lochhead

  4. Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Liebigstraße 13, 04103, Leipzig, Germany

    Geßner Reinhard

  5. Molecular Biology and Immunology Research Division, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, 305-0856, Japan

    Michiharu Sakurai

  6. Institute of Anatomy, Medical Faculty, University of Leipzig, Liebigstraße 13, 04103, Leipzig, Germany

    Albert M. Ricken

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  1. Claudia Merkwitz
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Correspondence to Albert M. Ricken.

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418_2010_775_MOESM1_ESM.pdf

Supplemental Figure S1. a to c Selective IHC staining of hematopoietic foetal liver cells (arrows) with anti-CD133 (a) and anti-CD34 antisera (b), and mAb N21 (c). d to f CD34 IHC staining of the endothelial lining of capillaries (d and e arrows) and larger blood vessels (f stars). g to j Staining of subsequent serial sections of foetal liver (g and h) and pancreas (i and j) with antigen pre-absorbed (preab, g and i) and native (h and j) anti-CD34 antiserum (AS). Pre-absorption of the antiserum blocks immunoreactivity with foetal liver (g) and pancreas (i) tissue. k and l Subsequent serial sections of foetal pancreas are probed with anti-CD34 antiserum pre-incubated with equimolar quantities of either CD34 antigen (k) or glucagon (l). Pre-incubation of the antiserum with glucagon, instead of specific antigen, results in prominent staining of acinar cells. Scale bars as indicated. (PDF 248 kb)

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Merkwitz, C., Pessa-Morikawa, T., Lochhead, P. et al. The CD34 surface antigen is restricted to glucagon-expressing cells in the early developing bovine pancreas. Histochem Cell Biol 135, 59–71 (2011). https://doi.org/10.1007/s00418-010-0775-x

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