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

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. 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE128407 | GEO | 2019/05/22

REPOSITORIES: GEO

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In vivo gene signature of TLR3KO mice stimulated by ethanol (EtOH) or all trans retinoic acid (atRA) 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 experiment is to investigate the profile of gene expression rescued by atRA in TLR3KO mice.

2019-05-22 | GSE128408 | GEO

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.

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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.

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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

Transcription profiling of human sebocytes (SEB-1) treated with 13-cis retinoic acid treatment

Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of cultured human immortalized sebocytes (SEB-1) treated with 13-cis RA was performed to gain insights into its sebocyte-specific mechanism of action. SEB-1 sebocytes were cultured with 0.1 uM 13-cis RA for 72 hours or vehicle control. Gene array expression profiling was conducted using Affymetrix HG-U95Av2 arrays in order to examine changes in gene expression as a result of treatment. A total of 85 genes (78 different genes) were significantly influenced by 13-cis RA: 58 were upregulated and 27 were down-regulated. There were changes in several genes involved in apoptosis and innate immunity. These studies are the first describing the sebocyte- specific response in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne. Experiment Overall Design: Total of 6 chips: 3 vehicle (DMSO) control and 3 13-cis RA (0.1 uM) treatment.

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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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13-cis retinoic acid treatment of human sebocytes (SEB-1)

Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of cultured human immortalized sebocytes (SEB-1) treated with 13-cis RA was performed to gain insights into its sebocyte-specific mechanism of action. SEB-1 sebocytes were cultured with 0.1 uM 13-cis RA for 72 hours or vehicle control. Gene array expression profiling was conducted using Affymetrix HG-U95Av2 arrays in order to examine changes in gene expression as a result of treatment. A total of 85 genes (78 different genes) were significantly influenced by 13-cis RA: 58 were upregulated and 27 were down-regulated. There were changes in several genes involved in apoptosis and innate immunity. These studies are the first describing the sebocyte- specific response in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne. Keywords: effects of 72 hour 13-cis RA treatment on cultured human sebocyte cells (SEB-1)

2008-03-04 | GSE10432 | 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

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