Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse

Abstract

In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds.

Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model

“…DTG and ELV were more capable in this activity. This last result acquires high relevance considering recent reports showing that forced expression of PPAR is able and sufficient to induce adipogenesis in fibroblasts [36] and that adipocytes can be reprogrammed into fibroblasts under transfection of some master regulators [38]. More recently, Jones et al [59] demonstrated that adipocytes could acquire a fibroblast-like transcriptional signature under over-feeding conditions.…”

“…Furthermore, in the last 20 years, some studies reported increased fibrosis in adipose tissue from PWH [34][35][36], and several mechanisms have been hypothesized. It has been described the increase of extracellular matrix in adipose tissue by deposition of collagen produced by adipocytes [35,37] and the reprogramming of adipocytes into fibroblast, confirmed by the expression of ER-TR7, a fibroblastic marker [38]. In addition, Ngono Ayissi et al [39] described the ability of BIC and DTG to induce a pro-fibrotic phenotype in simian beige adipose tissue and found this phenotype to be associated with insulin resistance.…”

Adipocyte differentiation of 3T3-L1 cells under TAF, TDF and INSTIs selective challenge: an in vitro model

“…DTG and EVT were more efficient in this activity. This last result acquires high relevance considering recent reports showing that forced expression of PPARɣ is able and sufficient to induce adipogenesis in fibroblasts [36] and that adipocytes can be reprogrammed into fibroblasts under transfection of some master regulators [38]. More recently, Jones et al demonstrated that adipocytes could acquire a fibroblast-like transcriptional signature by using a murine animal model under over-feeding conditions [50].…”

“…Furthermore, in the last 20 years, some studies reported increased fibrosis in adipose tissue from HIV-infected patients [34-36], and several mechanisms have been hypothesized to explain this phenomenon. It has been described the increase of extracellular matrix in adipose tissue by deposition of collagen produced by adipocytes [35, 37] and the reprogramming of adipocytes into fibroblast, confirmed by the expression of ER-TR7, a well-known fibroblastic marker was also reported [38]. In addition, more recently, Ngono et al described the ability of BIC and DTG to induce a pro-fibrotic phenotype in simian beige adipose tissue and found this phenotype to be associated with insulin resistance [39].…”