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In vivo gene signature of TLR3KO mice stimulated by ethanol (EtOH) or all trans retinoic acid (atRA) treatment

ABSTRACT: How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate entirely new hair follicles de novo following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor TLR3 to induce intrinsic retinoic acid (RA) synthesis in a gradient that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a novel stimulus for retinoic acid synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity. The goal of this experiment is to investigate the profile of gene expression rescued by atRA in TLR3KO mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE128408 | GEO | 2019/05/22

REPOSITORIES: GEO

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Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3

Project description:This SuperSeries is composed of the SubSeries listed below. How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.

2019-05-22 | GSE128868 | GEO

In vitro gene signature of cultured adult keratinocytes stimulated by all trans retinoic acid (atRA) and/or Poly I:C

Project description:How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate entirely new hair follicles de novo following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor TLR3 to induce intrinsic retinoic acid (RA) synthesis in a gradient that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a novel stimulus for retinoic acid synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity. Hand keratinocytes were treated with atRA (0.1 uM) and/or Poly I:C (0.1 ug/ml). RNA was extracted and sent for microarray analysis

2019-05-22 | GSE128407 | GEO

In vivo gene signature of human skin with CO2 laser treatment

Project description:How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate entirely new hair follicles de novo following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor TLR3 to induce intrinsic retinoic acid (RA) synthesis in a gradient that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a novel stimulus for retinoic acid synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity. The goal of this study is to investigate whole genome analysis in human skin with CO2 laser treatment, which leads to enhanced skin rejuvenation. Under Hopkins IRB (IRB00028768), 17 Caucasian women Fitzpatrick types I-III with average age of 55 and moderate to severe baseline photoaging were enrolled. Laser treatments and biopsy schedule were as listed, with treatments occurring both to the arm, and arm biopsies used for gene expression data listed.

2019-05-28 | GSE131789 | GEO

Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3

Project description:Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3

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Retinoic acid promotes tissue regeneration by resolving stem cell lineage plasticity

Project description:Stem cells upended from their niche upon injury display lineage plasticity, a transient multi-lineage state essential for tissue repair. Employing high-throughput approaches and three-dimensional cultures of hair follicle stem cells (HFSCs), we investigate the signals that govern the transition between homeostatic regeneration and lineage plasticity. We identify retinoic acid (RA) as a master orchestrator of HFSC behavior during these two processes. In the hair follicle, RA signals within defined niches and interacts with WNT and BMP cues to drive hair regeneration. In wounded skin, reduced RA signaling prompts HFSCs to prioritize epidermal re-epithelialization and must be restored to promote hair regrowth. Substantiated in vivo, our findings have profound therapeutic implications for hair growth and for chronic wounds and cancers, where lineage plasticity is unresolved.

2024-03-26 | GSE231731 | GEO

Less invasive diagnostics for cancer using hair follicle

Project description:Primary outcome(s): Comparison of the gene expression profile in hair follicle between cancer patients and healthy volunteer

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Functional stem cell aging dictated by skin tissue microenvironment

Project description:Organismal aging in mammals is manifested with architectural alteration and functional decline of multiple organs throughout the body. In aged skin, hairs are sparse, which has led to the hypothesis that the hair follicle stem cells (HFSCs) undergo epidermal differentiation during aging. Here, we employ single cell analysis to interrogate aging-related changes in the HFSCs. Unexpectedly, HFSCs maintain their lineage fidelity and show no signs of shifting to an epidermal fate. Despite maintaining lineage identity, HFSCs do show prevalent transcriptional changes in extracellular matrix genes. Of importance, these HFSC changes are accompanied by profound architectural perturbations in the aging stem cell niche. Upon surveying the dermis from young and aged skin, we also observe age-related changes in many non-epithelial cell types, including resident immune cells, sensory neurons, arrector pili muscles, and blood vessels – all of which have been previously associated with abilities to modulate hair follicle regeneration. Consistent with both intrinsic and extrinsic alterations in stem cell: niche communications, we find that in response to skin wounding, aged HFSCs repair the epidermis, but are defective in hair follicle regeneration. Intriguingly, whereas aged dermis cannot support young HFSCs, aged HFSCs can be rescued when supported by young dermis. Together, these findings favor a model where skin tissue microenvironment plays a dominant role in dictating the molecular properties and activities of HFSCs.

2019-12-31 | GSE124901 | GEO

mice，skin, iTRAQ

Project description:Wound Induced Hair Follicle neogenesis (WIHN) is a hair neogenesis phenomenon which occurred in the center of scar. Neonatal hair follicle are separated from the preexisting follicles by a hairless circular. We analysed the differentially expressed proteins between inner and outer area of scar at post-wound day 15 by iTRAQ technology.

2021-09-08 | PXD012868 | Pride

Gene expression in normal human epidermal keratinocytes treated with poly(I:C)

Project description:In a rare example akin to organogenesis in adult mammals, large wounds in mice lead to de novo morphogenesis of hair follicles. It is still not fully clear what controls this process, known as Wound Induced Hair Neogenesis (WIHN). In other tissues, prostaglandin E2 (PGE2) is an important effector of regeneration and has been shown to stimulate the Wnt/beta-catenin pathway, which in turn is known to control WIHN. Previously, our group has demonstrated that noncoding dsRNA released during wounding is both necessary and sufficient to stimulate WIHN through TLR3. Here, we hypothesize that dsRNA similarly induces the beta-catenin pathway through PGE2. We find that WIHN levels correlate closely to Wnt7b production in vivo, and that dsRNA potently induces Wnt7b in a manner that requires prostaglandin-endoperoxide synthase 2 (Ptgs2). The Ptgs2 inhibitor celecoxib reduces dsRNA-induced WIHN and Wnt7b, and exogenous PGE2 can rescue WIHN and Wnt7b. These results highlight noncoding dsRNA as a novel upstream coordinator of prostaglandin and Wnt levels in regeneration. We used microarrays to identify the human keratinocyte genes most upregulated or downregulated by poly(I:C)

2017-04-17 | GSE92646 | GEO

A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle.

Project description:The hair follicle is a biological oscillator that alternates growth, regression, and rest phases driven by the sequential activation of the proliferation/differentiation programs of resident stem cell populations. The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling, while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity. A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways. Here we have focused on the role of Endoglin (Eng), a key co-receptor for members of the Tgf-β/Bmp family of growth factors.Using an Eng haploinsufficient mouse model, we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell niches. We further report that β-catenin binds to the Eng promoter depending on Bmp signalling. Moreover, we show that β-catenin interacts with Smad4 in a Bmp/Eng-dependent context and both proteins act synergistically to activate Eng promoter transcription. These observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback crosstalk between Wnt/β-catenin and Bmp/Smad signals. Implication of Endoglin, Wnt/β-catenin and Bmp/Smad signals in the growth/rest hair follicle

2018-09-28 | GSE120556 | GEO

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