Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
Project description:While the regulatory landscape during stem cell differentiation has been well characterized, the shared and unique regulatory mechanisms in different ectodermally-derived epithelial cells have not been well described. Through defining the complement of super enhancers and typical enhancers in corneal epithelium for the first time, we show that regulatory regions are often shared between cell types of the same lineage, and that corneal super enhancers are already marked as potential regulatory domains in embryonic stem cells. Through the enrichment of KLF motifs in enhancers, we identified and defined a novel role for Kruppel family member KLF7 in promoting the corneal progenitor cell state, in many cases working antagonistically to corneal differentiation promoting KLF4. Our work highlights the importance of balance between proliferation and differentiation, both for proper tissue development and for homeostasis.
Project description:Analysis of change in transcriptosome after KLF4, KLF9, KLF11, KLF16 and KLF17 knockdown in hADSC. Analysis of effects of siRNA transfection (siCtrl, siKLF4, siKLF9, siKLF11, siKLF16 and siKLF17) in hADSC at gene expression level.The hypothesis tested in the present study was that different KLF members have distinctive roles in these cells.
Project description:KLF7, a member of the KLF family, is an evolutionarily conserved zinc finger-containing transcription factor. Previous studies demonstrated that KLF7 possesses diverse regulatory functions related to embryogenesis, cell growth, proliferation, and differentiation. Our results reveal that there was an increased abundance of KLF7 in OSM-treated HaCaT cells. Mechanistically, our results showed that OSM induces epidermal keratinocyte differentiation through phosphorylation of STAT5, which binds to the promoter and activates KLF7 transcription.
Project description:Pluripotency is the capacity to give rise to all differentiated cells of the body and the germ line and is governed by a self-reinforcing network of transcription factors. The forced expression of only some of these factors enables the reprogramming of somatic cells to pluripotency. In murine cells, several kruppel-like factors (KLFs) have been identified as stabilisers and inducers of pluripotency. Human somatic cells are routinely reprogrammed by expression of KLF4 in combination with OCT4, SOX2 and cMYC (OSKM). An extensive transcriptome analysis revealed, however, that KLF4 is barely expressed in conventional human pluripotent stem cells (PSCs). Here we show that KLF7 is robustly expressed in conventional human PSCs and it allows transcription factor-mediated somatic reprogramming. Moreover, we find that KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and boosts efficiency of chemical resetting to naive PSCs, overall suggesting that KLF7 is a general human pluripotency factor and an inducer of pluripotency.