Project description:Thymic epithelial cells (TECs) are essential for thymopoiesis and form a complex three-dimensional network, the organization of which is strikingly different from other epithelia. Interestingly, TECs express simple epithelia keratins in the cortex, stratified epithelia keratins in the medulla and epidermal differentiation markers in Hassall's bodies. Here we investigate the relationship between thymic epithelium and epidermal differentiation and show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured and cloned using conditions developed for epidermal cell therapy in human. Clonogenic TECs conserve a thymic identity and the capacity to integrate in a thymic epithelial network, but they acquire new functionalities when exposed to an inductive skin microenvironment, permanently adopting the fate of hair follicle multipotent stem cells. This change in fate, maintained over time in serial transplantation, correlates with a down-regulation of transcription factors important for thymic identity, and an up-regulation of epidermal markers. Consequently, the TECs’ capacity to integrate in a thymic epithelial network is altered or even lost. Our results demonstrate that the thymus contains a population of holoclone-like epithelial cells that can function as bona fide multipotent keratinocyte stem cells, and that microenvironmental cues are sufficient to re-direct epithelial-cell fate, allowing crossing of primitive germ layer boundaries from endoderm to ectoderm. Keywords: Cell type comparison
Project description:Here we have developed a novel FACS strategy to prospectively isolate hair follicle dermal stem cells, dermal sheath and dermal papilla cells from adult skin initiating synchronous hair follicle regeneration and identified Hic1 as a marker of hfDSCs and Rspondins as stimulators of hfDSCs and epithelial cells, and subsequently hair follicle regeneration
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grows downward to form transient-amplifying matrix progenitor cells. We used ChIP-seq to reveal the genome-wide maps of histone modifications underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation. Quiescent hair follicle stem cells (qHF-SCs), activated hair follicle stem cells (aHF-SCs) and transient-amplifying matrix cells (HF-TACs) were FACS-purified for ChIP-sequcencing.
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used RNA-seq to identify SOX9-dependent transcriptional changes and ChIP-seq to identify SOX9-bound genes in HF-SCs. Telogen quiescent hair follicle stem cells (HFSCs) and intefollicular epidermal cells (IFE) were FACS-purified for ChIP-sequcencing and HFSCs for RNA-Sequencing
Project description:Mammalian epidermis consists of three self-renewing compartments: the hair follicle, sebaceous gland and interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative to the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, while contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell. For the Lgr5 and Lgr6 stem cell comparison RNA was isolated from sorted GFPhi cell fractions of dorsal skin from Lgr5-EGFP-ires-CreERT2 mice and Lgr6-EGFP-ires-CreERT2, respectively (3 mice per group per sort).
Project description:Hair follicle (HF) regeneration begins when communication between quiescent epithelial stem cells (SCs) and underlying mesenchymal dermal papillae (DP) generates sufficient activating cues to overcome repressive BMP signals from surrounding niche cells. We uncovered a hitherto unrecognized DP transmitter, TGFβ2, which activates Smad2/3 transiently in HFSCs concomitant with entry into tissue regeneration. We used microarrays to detect the genes specifically affected by TGFß receptor II-deficient mice upon HFSC activation. Hair follicle stem cells (HFSCs) of hair gem (HG) and bulge, and total skin keratinocytes were FACS-purified from the mouse back skin at 2nd telogen-to-anagen transition stages.
