Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice
Young Jun Koh, Shinae Kang, Hyuek Jong Lee, Tae-Saeng Choi, Ho Sub Lee, Chung-Hyun Cho, Gou Young Koh
Young Jun Koh, Shinae Kang, Hyuek Jong Lee, Tae-Saeng Choi, Ho Sub Lee, Chung-Hyun Cho, Gou Young Koh
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Research Article

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.

Authors

Young Jun Koh, Shinae Kang, Hyuek Jong Lee, Tae-Saeng Choi, Ho Sub Lee, Chung-Hyun Cho, Gou Young Koh

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Figure 6

No GFP+perilipin+ adipocytes were detected in regenerative adipose tissues and wound-healing dermal tissue.

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No GFP+perilipin+ adipocytes were detected in regenerative adipose tissu...
(A–I) A proximal portion (20% of the total length) of the left-side epididymal adipose tissue of 8-week-old C57BL/6J mice that had received BMT from GFP+ mice 2 months before the dissection (dotted lines, A and E). The mice were fed a high-fat diet for the indicated periods. (B–D and F–I) Both sides of the epididymal adipose tissue from the mice were harvested, photographed, and immunostained for perilipin (red stain) and PECAM-1 (blue stain) of the dissected region of the left epididymal adipose tissue (A and E, boxed regions). Some clustered GFP+ cells (green stain) looked like unilocular adipocytes (B and C), but the sequential dissected images of this portion (boxed region in C) revealed smaller and clustered GFP+perilipin– cells (D). No GFP+perilipin+ adipocytes were detected in the adipose tissues. (J–S) Hole-punch injuries made in the ears of 8-week-old C57BL/6J mice that had received BMT from GFP+ mice 2 months before and were then fed a high-fat diet for the indicated times. Ears from the mice were harvested and photographed, and immunostained for perilipin and PECAM-1 at the healing region of ear (J and O, boxed regions). (K–N and P–S) No GFP+ cells were perilipin+ adipocytes in the wound-healing dermal tissues after the injury. Scale bars: 100 μm.