Wound infiltrating adipocytes are not myofibroblasts

Gopal, Shruthi Kalgudde; Dai, Ruoxuan; Stefanska, Ania; Ansari, Meshal; Zhao, Jiakuan; Ramesh, Pushkar; Bagnoli, Johannes W.; Correa-Gallegos, Donovan; Lin, Yunfeng; Christ, Simon; Angelidis, Ilias; Lupperger, Valerio; Marr, Carsten; Davies, Lindsay C.; Enard, Wolfgang; Machens, Hans‐Günther; Schiller, Herbert B.; Jiang, Dongsheng; Rinkevich, Yuval

doi:10.1038/s41467-023-38591-6

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Adipocyte dedifferentiation is suggested to contribute to wound healing in two ways: first by releasing lipids that promote macrophage infiltration necessary for early wound healing, and second as a source of myofibroblasts that generate and remodel scar tissue (Shook et al, 2020). However, the process of adipocytes changing cellular identity into fibrogenic cells has been called into question (Kalgudde Gopal et al, 2023). Our results demonstrate that most Pdgfra + adipocytes remain at the wound edge and do not migrate into the wound bed, but we also found aSMA expression in labeled cells at the wound center.…”

Section: Discussionmentioning

confidence: 99%

“…Many cytokine and growth factor receptors are upregulated by dedifferentiated adipocytes in skin wounds, including receptors for PDGF and TGFb (Shook et al, 2020), but whether these signals regulate dedifferentiation is unknown. More recently, the process of adipocyte dedifferentiation has been questioned by some investigators (Kalgudde Gopal et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of adipocyte dedifferentiation at the skin wound edge

Yao,

Jeong,

Kwon

et al. 2023

Preprint

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Adipocytes have diverse roles in energy storage and metabolism, inflammation, and tissue repair. Mature adipocytes have been assumed to be terminally differentiated cells. However, recent evidence suggests that adipocytes retain substantial phenotypic plasticity, with potential to dedifferentiate into fibroblast-like cells under physiological and pathological conditions. Here, we develop a two-step lineage tracing approach based on the observation that fibroblasts express platelet-derived growth factor receptor alpha (Pdgfra) while adipocytes express Adiponectin (Adipoq) but notPdgfra. Our approach specifically tracesPdgfra+cells that originate fromAdipoq+adipocytes. We find many traced adipocytes and fibroblast-like cells surrounding skin wounds, but only a few traced cells localize to the wound center. In agreement with adipocyte plasticity, traced adipocytes incorporate EdU, downregulate Plin1 and PPARγ, and upregulate αSMA. We also investigate the role of potential dedifferentiation signals using constitutively active PDGFRα mutation,Pdgfraknockout, orTgfbr2knockout models. We find that PDGF and TGFβ signaling both promote dedifferentiation, and PDGFRα does so independently of TGFβR2. These results demonstrate an intersectional genetic approach to trace the hybrid cell phenotype ofPdgfra+adipocytes, which may be important for wound repair, regeneration and fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of adipocyte dedifferentiation at the skin wound edge

Yao,

Jeong,

Kwon

et al. 2023

Preprint

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“…The Rinkevich lab has challenged the conversion of lineage traced mature dermal adipocyte to profibrotic fibroblast at a functional level. They use a combination transcriptome analysis in an ex vivo skin wounding model and transplant experiments in vivo to demonstrate that the adipocyte to fibroblasts conversion occurs transiently by morphology, but the transcriptome and function remain distinct from fibrogenic fibroblasts during wound healing 149 …”

Section: Lipid Depletionmentioning

confidence: 99%

Tissue fibrosis associated depletion of lipid‐filled cells

Jussila,

Zhang,

Kirti

et al. 2024

Experimental Dermatology

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Fibrosis is primarily described as the deposition of excessive extracellular matrix, but in many tissues it also involves a loss of lipid or lipid‐filled cells. Lipid‐filled cells are critical to tissue function and integrity in many tissues including the skin and lungs. Thus, loss or depletion of lipid‐filled cells during fibrogenesis, has implications for tissue function. In some contexts, lipid‐filled cells can impact ECM composition and stability, highlighting their importance in fibrotic transformation. Recent papers in fibrosis address this newly recognized fibrotic lipodystrophy phenomenon. Even in disparate tissues, common mechanisms are emerging to explain fibrotic lipodystrophy. These findings have implications for fibrosis in tissues composed of fibroblast and lipid‐filled cell populations such as skin, lung, and liver. In this review, we will discuss the roles of lipid‐containing cells, their reduction/loss during fibrotic transformation, and the mechanisms of that loss in the skin and lungs.

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“…Tissue regeneration requires adipocyte-dependent communication for the repair of damaged tissues [ 66 , 67 ]. Adipocytes residing in the hypodermis undergo lipolysis to efficiently recruit macrophages during inflammation.…”

Section: Role Of the Hypodermis In Skin Homeostasismentioning

confidence: 99%

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

Liu,

Lu,

Feng

2024

Cell Death Dis

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Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

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Wound infiltrating adipocytes are not myofibroblasts

Cited by 7 publications

References 53 publications

Regulation of adipocyte dedifferentiation at the skin wound edge

Regulation of adipocyte dedifferentiation at the skin wound edge

Tissue fibrosis associated depletion of lipid‐filled cells

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function

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