Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice

Abstract

Little is known about whether bone marrow-derived circulating progenitor cells (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a role in expanding adipocyte number during adipose tissue growth. Using a mouse bone marrow transplantation model, we addressed whether BMDCPCs can transdifferentiate into adipocytes under standard conditions as well as in the settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF. We also addressed the possibility of transdifferentiation to adipocytes in a murine parabiosis model. In each of these settings, our findings indicated that BMDCPCs did not transdifferentiate into either unilocular or multilocular adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic macrophages in adipose tissues--which resembled transdifferentiated multilocular adipocytes by appearance, but displayed cell surface markers characteristic for macrophages - in the absence of adipocyte marker expression. When exposed to adipogenic medium in vitro, bone marrow cells differentiated into multilocular, but not unilocular, adipocytes, but transdifferentiation was not observed in vivo, even in the contexts of adipose tissue regrowth or dermal wound healing. Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in vivo and play little, if any, role in expanding the number of adipocytes during the growth of adipose tissues.

Characterization of Human Adipose Tissue-Resident Hematopoietic Cell Populations Reveals a Novel Macrophage Subpopulation with CD34 Expression and Mesenchymal Multipotency

“…This suggests that both ASCs and macrophages have substantial plasticity and are closely related to each other. In addition, some studies suggest that certain adipocytes and adipose progenitor cells originate from bone marrow-derived cells [44][45][46], although there was a contradictory report that failed to demonstrate transdifferentiation of bone marrow-derived cells into adipocytes [47]. Our study demonstrated high adipogenic differentiation capacity of CD34 + /CD206…”

Regional differences in cellular mechanisms of adipose tissue gain with overfeeding

“…Newly formed mature adipocytes arise from preadipocytes, progenitors that are, for the most part, resident in fat depots (23)(24)(25)(26). Preadipocytes in abdominal s.c. fat are distinct from those in mesenteric or omental fat, differing in proliferative potential, replicative subtype abundance, capacity for adipogenesis, susceptibility to apoptosis, and gene-expression profiles (6, 13, 27, 28).…”

Heterogeneity of adipose tissue in development and metabolic function

“…Therefore, bone-marrow-derived adipocytes may account in part for the detrimental changes in adipose metabolism and inflammation with aging and obesity (Majka et al, 2010). However, the significance of these findings has been questioned by others given that several studies did not observe a significant contribution of bone-marrow-derived progenitors to adipogenesis (Berry and Rodeheffer, 2013;Koh et al, 2007;Tomiyama et al, 2008).…”