Abstract
Cellular plasticity is a transformation of a terminally differentiated cell into another cell type, which has been long known to occur in disease and regeneration. However, white adipocytes (fat cells) have only recently been observed to undergo different types of cellular plasticity. Adipocyte transdifferentiation into myofibroblasts and cancer-associated fibroblasts occurs in fibrosis and cancer, respectively. On the other hand, reversible adipocyte dedifferentiation into adipocyte progenitor cells (preadipocytes) has been demonstrated in mammary gland and in dermal adipose tissue. Here we discuss the research on adipocyte plasticity, including the experimental approaches that allowed to detect and study it, the current state of the knowledge, major research questions which remain to be addressed, and the advances required to stimulate adipocyte plasticity research. In the future, the knowledge of the molecular mechanisms of adipocyte plasticity can be utilized both to prevent adipocyte plasticity in disease and to stimulate it for use in regenerative medicine.
Highlights
In the traditional view of cell differentiation, cells follow a differentiation trajectory in discrete developmental stages, beginning with stem cells and culminating with a terminally differentiated state [1]
Given that cellular plasticity allows for cells to transfer into ontogenically close lineages, one would expect that white adipocytes may be able to give rise to other mesenchymal cell types, such as muscle cells or osteoblasts, which would make them an important potential cellular source for regeneration medicine, especially since large numbers of adipocytes can be obtained during a biopsy [66]
Whether DFAT cells are a product of white adipocyte plasticity or not, their use for regenerative purposes is an exciting avenue of research [74]
Summary
In the traditional view of cell differentiation, cells follow a differentiation trajectory in discrete developmental stages, beginning with stem cells and culminating with a terminally differentiated state [1]. While many categories of cellular plasticity have been proposed, here we will distinguish between dedifferentiation, which involves a differentiated cell reverting to a cell with a greater developmental potential, such as a stem or progenitor cell, and transdifferentiation, in which a differentiated cell transfers into another differentiated cell type (Figure 1). Novel experimental approaches allow to induce cellular plasticity through reprogramming of differentiated cells—in the most prominent example, to obtain induced pluripotent stem cells (iPCSs) from fibroblasts [5]. Adipose (fat) tissue is a major endocrine organ whose primary function is the long-term storage of energy in the form of lipids. It is distributed across multiple depots in the body and is comprised of fat cells (adipocytes), adipose progenitor cells, and other non-adipogenic cell types, including fibroblasts, endothelial cells, and neurons. The Extent of White Adipocyte Plasticity in Physiological Processes and in Disease
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