Extensive elimination of acinar cells during normal postnatal pancreas growth
Miri Stolovich-Rain,
Ori Fridlich,
Shira Azulai,
Agnes Klochendler,
Shira Anzi,
Judith Magenheim,
Ilan Stein,
Fatima Mushasha,
Benjamin Glaser,
Eli Pikarsky,
Danny Ben-Zvi,
Yuval Dor
Affiliations
Miri Stolovich-Rain
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Ori Fridlich
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Shira Azulai
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Agnes Klochendler
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Shira Anzi
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Judith Magenheim
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Ilan Stein
The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Fatima Mushasha
The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Benjamin Glaser
Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Eli Pikarsky
The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Danny Ben-Zvi
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel
Yuval Dor
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel; Corresponding author
Summary: While programmed cell death plays important roles during morphogenetic stages of development, post-differentiation organ growth is considered an efficient process whereby cell proliferation increases cell number. Here we demonstrate that early postnatal growth of the pancreas unexpectedly involves massive acinar cell elimination. Measurements of cell proliferation and death in the human pancreas in comparison to the actual increase in cell number predict daily elimination of 0.7% of cells, offsetting 88% of cell formation over the first year of life. Using mouse models, we show that death is associated with mitosis, through a failure of dividing cells to generate two viable daughters. In p53-deficient mice, acinar cell death and proliferation are reduced, while organ size is normal, suggesting that p53-dependent developmental apoptosis triggers compensatory proliferation. We propose that excess cell turnover during growth of the pancreas, and presumably other organs, facilitates robustness to perturbations and supports maintenance of tissue architecture.
