Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Shin, Sunhye; Pang, Yiyu; Park, Jooman; Liu, Lifeng; Lukas, Brandon; Kim, Seung Hyeon; Xu, Pingwen; Berry, Daniel C.; Jiang, Yuwei

doi:10.7554/elife.56189

Cited by 43 publications

(27 citation statements)

References 59 publications

(102 reference statements)

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“…Another group used PDGFRα-Cre-ER T2 mice generated by Rivers et al. [ 47 ] and showed that PDGFRα + APs did not participate in adult adipogenesis [ 48 ]. These studies were performed in different laboratories using different doses of TAM for recombination and with distinct Cre-drivers for producing transgenic models.…”

Section: Discussionmentioning

confidence: 99%

Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet

Bilal

Nawaz

Kado

et al. 2021

Molecular Metabolism

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Objective Expansion of adipose tissue during obesity through the recruitment of newly generated adipocytes (hyperplasia) is metabolically healthy, whereas that through the enlargement of pre-existing adipocytes (hypertrophy) leads to metabolic complications. Accumulating evidence from genetic fate mapping studies suggests that in animal models receiving a high-fat diet (HFD), only adipocyte progenitors (APs) in gonadal white adipose tissue (gWAT) have proliferative potential. However, the proliferative potential and differentiating capacity of APs in the inguinal WAT (iWAT) of male mice remains controversial. The objective of this study was to investigate the proliferative and adipogenic potential of APs in the iWAT of HFD-fed male mice. Methods We generated PDGFRα-GFP-Cre-ER T2 /tdTomato (KI/td) mice and traced PDGFRα-positive APs in male mice fed HFD for 8 weeks. We performed a comprehensive phenotypic analysis, including the histology, immunohistochemistry, flow cytometry, and gene expression analysis, of KI/td mice fed HFD. Results Contrary to the findings of others, we found an increased number of newly generated tdTomato + adipocytes in the iWAT of male mice, which was smaller than that observed in the gWAT. We found that in male mice, the iWAT has more proliferating tdTomato + APs than the gWAT. We also found that tdTomato + APs showed a higher expression of Dpp4 and Pi16 than tdTomato − APs, and the expression of these genes was significantly higher in the iWAT than in the gWAT of mice fed HFD for 8 weeks. Collectively, our results reveal that HFD feeding induces the proliferation of tdTomato + APs in the iWAT of male mice. Conclusion In male mice, compared with gWAT, iWAT undergoes hyperplasia in response to 8 weeks of HFD feeding through the recruitment of newly generated adipocytes due to an abundance of APs with a high potential for proliferation and differentiation.

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Section: Discussionmentioning

confidence: 99%

Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet

Bilal

Nawaz

Kado

et al. 2021

Molecular Metabolism

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“…In contrast, FGF13 inhibited myogenic differentiation of C2C12 myoblasts by activating ERK1/2 signaling [ 63 ]. Different from functions of the above genes in myogenesis, PDGFRα + mesenchymal progenitors were the major contributor to ectopic fat formation in skeletal muscle [ 37 ], and embryonic adipose progenitor cells without PDGFRα would undergo fate change from adipogenic to fibrotic lineage [ 64 ]. Although DNA methylation-induced PDGFRα and FGFR2 silencing has been reported in CG4 cells [ 65 ] or primary human pituitary adenomas [ 66 ], the role of DNA methylation in regulating the expression level of these co-different genes and their effects on myogenesis or adipogenesis still remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

Zhang

Sun

et al. 2020

Stem Cell Res Ther

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Background Skeletal muscle is a complex and heterogeneous tissue accounting for approximately 40% of body weight. Excessive ectopic lipid accumulation in the muscle fascicle would undermine the integrity of skeletal muscle in humans but endow muscle with marbling-related characteristics in farm animals. Therefore, the balance of myogenesis and adipogenesis is of great significance for skeletal muscle homeostasis. Significant DNA methylation occurs during myogenesis and adipogenesis; however, DNA methylation pattern of myogenic and adipogenic precursors derived from skeletal muscle remains unknown yet. Methods In this study, reduced representation bisulfite sequencing was performed to analyze genome-wide DNA methylation of adipogenic and myogenic precursors derived from the skeletal muscle of neonatal pigs. Integrated analysis of DNA methylation and transcription profiles was further conducted. Based on the results of pathway enrichment analysis, myogenic precursors were transfected with CACNA2D2-overexpression plasmids to explore the function of CACNA2D2 in myogenic differentiation. Results As a result, 11,361 differentially methylated regions mainly located in intergenic region and introns were identified. Furthermore, 153 genes with different DNA methylation and gene expression level between adipogenic and myogenic precursors were characterized. Subsequently, pathway enrichment analysis revealed that DNA methylation programing was involved in the regulation of adipogenic and myogenic differentiation potential through mediating the crosstalk among pathways including focal adhesion, regulation of actin cytoskeleton, MAPK signaling pathway, and calcium signaling pathway. In particular, we characterized a new role of CACNA2D2 in inhibiting myogenic differentiation by suppressing JNK/MAPK signaling pathway. Conclusions This study depicted a comprehensive landmark of DNA methylome of skeletal muscle-derived myogenic and adipogenic precursors, highlighted the critical role of CACNA2D2 in regulating myogenic differentiation, and illustrated the possible regulatory ways of DNA methylation on cell fate commitment and skeletal muscle homeostasis.

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“…Next, we used platelet-derived growth factor receptor α (PDGFR-α) and α smooth muscle actin (α-SMA) antibodies to identify mesenchymal stromal cells that produce ECM and play important roles in wound healing of subcutaneous tissue of the skin 28 . PDGFR-α is a cell surface receptor tyrosine kinase expressed in mesenchymal stromal cells in a variety of tissues and is also used as a marker for adipose progenitor cells [29][30][31][32] . Immunohistochemical analysis indicated that PDGFR-α-positive cells were located along the panniculus carnosus layer in the wound region, and α-SMA-positive cells were located on the panniculus carnosus layer at the wound edge in Lepr db/+ mice.…”

Section: Resultsmentioning

confidence: 99%

Altered regulation of mesenchymal cell senescence promotes pathological changes associated with diabetic wound healing

Kita

Saito

Miura

et al. 2021

Preprint

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Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes physiological wound process; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. In this study, we demonstrate that the number of p15INK4B + senescent PDGFR-α + mesenchymal cells in adipose tissue transiently increases in early phases of wound healing in non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in wound healing impairment and an alteration in the cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results give novel insight into how regulation of senescence in adipose tissue contributes to the wound healing process and provide the basis for the development of therapeutic approaches for wound healing impairment in diabetes.

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Dynamic control of adipose tissue development and adult tissue homeostasis by platelet-derived growth factor receptor alpha

Cited by 43 publications

References 59 publications

Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet

Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet

Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

Altered regulation of mesenchymal cell senescence promotes pathological changes associated with diabetic wound healing

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