Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland

Author:

Morroni Manrico1,Giordano Antonio1,Zingaretti Maria Cristina1,Boiani Romina1,De Matteis Rita1,Kahn Barbara B.1,Nisoli Enzo1,Tonello Cristina1,Pisoschi Catalina1,Luchetti Michele M.1,Marelli Mariella1,Cinti Saverio1

Affiliation:

1. Institutes of Anatomy and Internal Medicine, School of Medicine, University of Ancona, Via Tronto 10/A, 60020 Ancona, Italy; Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215; Center for Study and Research on Obesity, Laboratorio Interdisciplinare Tecnologie Avanzate Vialba, Luigi Sacco Hospital, Via G. B. Grassi 74, 20157 Milan, Italy; and University of Medicine and Pharmacy, Stradã Petru Rares̊ 4, 200349 Craiova 1100, Romania

Abstract

Mammalian breast adipose tissue is replaced by a milk-secreting gland during pregnancy; the reverse process takes place upon interruption of lactation. Morphological and bromodeoxyuridine studies provide indirect evidence that mouse mammary adipocytes transform into secretory epithelial cells during pregnancy and revert to adipocytes after lactation. By using the Cre-loxP recombination system we show that the mammary gland of whey acidic protein (WAP)- Cre / R26R mice, in which secretory epithelial cells express the lacZ gene during pregnancy, contains labeled adipocytes during involution. Conversely, adipocyte P2- Cre / R26R mice, in which adipocytes are labeled before pregnancy, contain labeled secretory epithelial cells during pregnancy. We conclude that reversible adipocyte-to-epithelium and epithelium-to-adipocyte transdifferentiation occurs in the mammary gland of adult mice during pregnancy and lactation.

Publisher

Proceedings of the National Academy of Sciences

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