Wnt/β-catenin Signaling Pathway Promotes Transdifferentiation from Fetal Skin Fibroblasts to Keratinocyte-like Cells

Background: Wound healing is a dynamic, sequential,and complex physiological process, including a variety of cellular events, such as proliferation, adhesion, chemotaxis, and apoptosis. Skin fibroblasts and keratinocytes are the two most important cells involved in wound repair, and Relying on the proliferation and differentiation of keratinocytes to form epithelium to completely cover the wound is the most ideal result for wound repair, so expanding the source of keratinocytes is a huge challenge. In this study, we examined the phenomenon that fetal skin fibroblasts spontaneously transdifferentiated into keratinocyte-like cells in conventional culture, and evaluated the characteristics of KLCs and the potential mechanisms of the transdifferentiation process.Methods: HFF-1 were routinely cultured in ordinary DMEM medium for more than 40 days,and observed the cell morphology. The cytological properties of KLCs at the cellular and molecular levels were detected by RT-PCR, Western-blot, immunofluorescence, Transwell, and cell scratch experiments.The functionality and safety of KLCs were determined through wound healing and tumorigenicity experiments. And high-throughput transcriptome sequencing (RNA-seq) was performed to explore the mechanism underlying HFF-1 transdifferentiation.Results: The transdifferentiation process started on the 25th day and was completed by the 40th day. KLCs and KCs had similar expressions at the molecular and protein levels, both functioned similarly in wound healing and were non-tumorigenic.RNA-seq revealed that the transdifferentiation process was regulated by the activation of the classical Wnt/β-catenin signaling pathway, which could shorten the process to 10 days.Conclusion: This study demonstrates that HFF-1 can spontaneously transdifferentiate into KLCs with conventional culture conditions, and the Wnt/β-catenin signaling pathway regulates the transdifferentiation process.

The molecular and phenotypic makeup of fetal human skin T lymphocytes

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation, however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence we found a large population with a naive and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.

Transitory Fetal Skin Edema in a Pregnant Patient with a Mild SARS-CoV-2 Infection

Background. Vertical transmission of the Coronavirus Disease 2019 (COVID-19) is still controversial. Additionally, the consequences of the infection during pregnancy in the offspring also are unknown. Case. A transitory fetal skin edema and polyhydramnios have been demonstrated by ultrasound in a pregnant patient with COVID-19 after a negative RT-PCR for SARS-CoV-2. The fetal findings presented a spontaneous resolution in utero, and abnormal findings were not found in the newborn. Conclusion. Women who have undergone SARS-CoV-2 infection during pregnancy should receive a subsequent appropriate follow-up in order to clarify the fetal consequences of the novel coronavirus, if any.

αβγδ T cells play a vital role in fetal human skin development and immunity

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor–ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

A wonderful case of permission foetu in foetu

In 1859 (? Is it a typo?) The author had to accept a baby, normally built with the exception of the following rare anomaly: the baby was born as if sitting astride a ball. Anus is missing; the sac, formed by the continuation of the fetal skin, occupies the buttocks and the back of the thighs to the scrotum and goes down to the middle of the legs. The skin that forms the membrane of this sac is of normal thickness and bluish-reddish color, depending on the bloody-serum contents of the bag and on the abundantly developed veins.

The anti-fibrotic effect of human fetal skin-derived stem cell secretome on the liver fibrosis

Background: Liver fibrosis resulting from a chronic liver injury is one of the significant causes of mortality. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease while maintaining its advantages over the current therapies. Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFSSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSCs secretome in liver fibrosis, we established the CCl4-induced liver fibrosis rat model, and we administered hFSSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFSSCs secretome effectively reduced collagen content in the liver, and improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSCs secretome reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSC secretome inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, while we observed, increased Smad7 expression. Conclusions: In conclusion, our results suggest that hFSSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

The Anti-fibrotic Effect of Human Fetal Skin-derived Stem Cell Secretome on the Liver Fibrosis

Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages.Methods: In this study, we investigated the effect ofhuman fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCssecretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCssecretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCssecretome in hepatic stellate cells (HSCs).Results: Our results showed that hFFSCssecretomeffectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found thathFFSCssecretom reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSCsecretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression.Conclusions: In conclusions, our results suggest that hFFSCssecretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

Developing human fetal skin demonstrates a unique lymphocyte signature

SummaryLymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity, demonstrating a unique fetal skin lymphocyte signature. While most conventional αβ T (Tconv) cells in fetal skin have a naïve, proliferative phenotype, a subset of CD4+ Tconv and CD8+ cells demonstrate memory-like features and a propensity for IFNγ production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin Tregs demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encounters in utero and in infancy.