Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation

Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation and the developmental origin of the re-appearing adipocyte post involution are unclear. Here, we reveal that adipocytes in the mammary gland de-differentiate into Pdgfrα⁺ preadipocyte- and fibroblast-like cells during pregnancy and remain de-differentiated during lactation. Upon weaning, de-differentiated fibroblasts proliferate and re-differentiate into adipocytes. This cycle occurs over multiple pregnancies. These observations reveal the potential of terminally differentiated adipocytes to undergo repeated cycles of de-differentiation and re-differentiation in a physiological setting. Adipocytes in the mammary gland disappear during lactation. Wang et al. show that these mammary adipocytes fully de-differentiate into preadipocytes during lactation and readily re-differentiate during involution. The same adipocytes are therefore “recycled” over multiple rounds of pregnancies. De-differentiation constitutes a new possible fate for terminally differentiated adipocytes.