Abstract
Several studies have reported inducing adult cells into sweat gland-like cells; however, slow transition and low efficiency limit the potential for cell-based treatment. Here, we show that overexpression of the transcription factor FoxC1 was sufficient to reprogram epidermal cells to induced functional sweat gland-like cells (iSGCs). The iSGCs expressing secreting-related genes, had a global gene expression profile between fetal SGCs (P5) and adult SGCs (P28). Moreover, iSGCs transplanted into the burn mice model facilitated wound repair and sweat gland regeneration. We further demonstrated that the Foxc1 upregulated BMP5 transcription and BMP5 is responsible for the cell-type transition. Collectively, this study shows that lineage reprogramming of epidermal cells into iSGCs provides an excellent cell source and a promising regenerative strategy for anhidrosis and hypohidrosis.
Highlights
Millions of sweat glands (SGs) are spread over the human body and sweating is indispensable for the maintenance of human body temperature[1]
The stratified epidermis, spindle-like cell morphology, rapid proliferation, and K5K14 expression means that epidermal cells retain stemness, while single-duct and short-coiled secretion part, clustered cells slow down cycling, and K8, K18, K19, and CEA expression shows sweat gland specification (Fig. 1)
We identified 32 transcription factors (TFs) (Fig. S2) that were upregulated in the specification of SG fate and selected a subset of three TFs (FoxC1, Irf[6], and Tfcp2l1) on the basis of their known roles during epidermis development or their ability to enhance gland morphogenesis when expressed in the ectoderm for further functional analysis[17,18,19,20,21,22]
Summary
Millions of sweat glands (SGs) are spread over the human body and sweating is indispensable for the maintenance of human body temperature[1]. Someone converted fibroblasts into SGCs successfully with TF NF-kB and Lef-1, but the inductive efficiency is limited and the underlying mechanism is unrevealed[11]. As both epidermal cells (ECs) and SGCs were developed from epidermal progenitors, the similarity between ECs and SGCs on the molecular level implicated further that ECs are a potential cell source for SGC reprogramming and in vivo treatment of a large scale of traumatic injury recovered with less effort of lineage transition[12,13]
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