Leptin receptor marks and targets the hair follicle mesenchymal niche
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA673418 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12952961_1.fastq.gz | Fastqsanger.gz | |||
| SRR12952961_2.fastq.gz | Fastqsanger.gz | |||
| SRR12952962_1.fastq.gz | Fastqsanger.gz | |||
| SRR12952962_2.fastq.gz | Fastqsanger.gz | |||
| SRR12952963_1.fastq.gz | Fastqsanger.gz |
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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).
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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.
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Project description:While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment.
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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.
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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.
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