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Noncoding dsRNA induces Retinoic Acid synthesis to stimulate regeneration

ABSTRACT: We uncover a novel mechanism whereby developmental pathways are reactivated in adults to promote regeneration.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin

SUBMITTER: Weiliang Huang

LAB HEAD: Maureen Kane

PROVIDER: PXD013854 | Pride | 2019-05-23

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	LG_Keratinocytes_Proteomics_Expression_WH12-27-2017.xlsx	Xlsx
	LG_Skin_Center_Edge_800ng_3-15-2018_C3.raw	Raw
	LG_Skin_Center_Edge_800ng_3-15-2018_C4.raw	Raw
	LG_Skin_Center_Edge_800ng_3-15-2018_C5.raw	Raw
	LG_Skin_Center_Edge_800ng_3-15-2018_E3.raw	Raw

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Publications

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

Kim Dongwon D Chen Ruosi R Sheu Mary M Kim Noori N Kim Sooah S Islam Nasif N Wier Eric M EM Wang Gaofeng G Li Ang A Park Angela A Son Wooyang W Evans Benjamin B Yu Victoria V Prizmic Vicky P VP Oh Eugene E Wang Zixiao Z Yu Jianshi J Huang Weiliang W Archer Nathan K NK Hu Zhiqi Z Clemetson Nashay N Nelson Amanda M AM Chien Anna A Okoye Ginette A GA Miller Lloyd S LS Ghiaur Gabriel G Kang Sewon S Jones Jace W JW Kane Maureen A MA Garza Luis A LA

Nature communications 20190626 1

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 predic ...[more]

PMID: 31243280

Similar Datasets

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

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 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.

| S-EPMC6594970 | biostudies-literature

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

microRNA expression in skin and wound edge tissue at different time points

Project description:Change in miRNA expression pattern during different phases of wound healing following full thickness excisional wounding was studied. In the study presented here, a comprehensive profiling of all the mouse/rat miRs annotated in the miRBase 8.0 was performed using the FlexmiRM-bM-^DM-" MicroRNA Labeling Kit

2014-03-06 | E-GEOD-55661 | biostudies-arrayexpress

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

| PRJNA529187 | ENA

Bulk-cell RNA-seq analysis of early cutaneous wound healing in mouse

Project description:To study early-onset gene expression changes in cutaneous wound healing, 3 mm wounds were induced into the back skin of female wildtype C57BL/6 mice using a biopsy punch. Mice were sacrificed 2h, 6h or 24h post wound induction (PWI) and 1 - 1.5 mm of skin lining the wound edge was isolated and sequenced. The skin from the initial punch biopsy (0h PWI) was preserved and taken as a control sample to identify differentially expressed genes.

2018-07-31 | E-MTAB-6686 | biostudies-arrayexpress

After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration.

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 is an important effector of regeneration and has been shown to stimulate the Wnt/β-catenin pathway, which in turn is known to control WIHN. Previously, our group has shown that noncoding double-stranded RNA (dsRNA) released during wounding is both necessary and sufficient to stimulate WIHN through toll-like receptor 3. Here, we hypothesized that dsRNA similarly induces the β-catenin pathway through prostaglandin E2. We found that WIHN levels correlate closely with Wnt7b production in vivo and that dsRNA potently induces Wnt7b in a manner that requires Ptgs2. The Ptgs2 inhibitor celecoxib reduces dsRNA-induced WIHN and Wnt7b, and exogenous prostaglandin E2 can rescue WIHN and Wnt7b. Although other Wnts and pathways likely contribute, these results highlight noncoding dsRNA as an upstream coordinator of prostaglandin and Wnt levels in regeneration.

| S-EPMC5483387 | biostudies-literature

Expression data from wound skin taken at three time points post wounding

Project description:The full complement of hair follicles is generated during embryogenesis. Normally, no new hair is created after this time. Large full thickness skin excision wounding can result in the generation of new hair in the adult. Placodes can be observed following complete reepithelialization at wound day 14. The events leading to hair neogenesis following wounding remain poorly understood. Late healing events (from wound day 10 to wound day 14) provide a possible window of induction for hair regeneration. We used microarrays to analyse changes in gene expression during late skin healing to provide candidates for factors involved in hair neogenesis following wounding. 6 week old C57Bl/6 mice received large full thickness skin excisions. Healing wound tissue was excised at wound day 10, 12 or 14 and analyzed for gene expression.

2013-09-01 | E-GEOD-46244 | biostudies-arrayexpress

Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [skin wound]

Project description:Transcriptional coactivator Mediator complex facilitates transcription of various transcription factors. Previously, we have generated Med1 conditional null mice, where a critical subunit of Mediator, Med1, is removed from keratinocytes. Here we present evidence that ablation of Med1 accelerated epidermal regeneration after injury. As bulge keratinocyte stem cells are important contributors to regenerate epidermis, we first analyzed properties of stem cells in Med1 null mice. BrdU long retaining analysis revealed that deletion of Med1 still maintained quiescence of bulge keratinocyte stem cells, despite of general hyperplasia observed in Med1 deficient keratinocytes. Gene expression analysis demonstrated that a series of niche matrix proteins decreased in Med1 deficient keratinocytes. In contrast, the expression of stem cell marker Sox9 was not altered, suggesting stem cells are present but activated because of abnormal niche surrounding stem cells. In addition, Med1 deletion suppressed injury induced inflammatory reaction, which indirectly regulates epidermal regeneration. We also indicated that TGFβ1 significantly decreased in both bulge and epidermal keratinocytes upon Med1 deletion. Our study demonstrates that coactivator Med1 has a critical role to maintain bulge stem cells and epidermal regeneration presumably through regulation in TGFβ signaling. n=3 WT and KO (each sample contain RNA isolated from wounded or nonwounded skins excised from 3 mice)

2014-01-01 | E-GEOD-50670 | biostudies-arrayexpress

Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-01 | E-GEOD-50673 | biostudies-arrayexpress

CD14 Is Induced by Retinoic Acid and Is Required for Double Stranded Noncoding RNA-Induced Regeneration.

Project description: Not available

| S-EPMC9259758 | biostudies-literature