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      Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration

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          Abstract

          Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.

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          Most cited references106

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

            Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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              HISAT: a fast spliced aligner with low memory requirements.

              HISAT (hierarchical indexing for spliced alignment of transcripts) is a highly efficient system for aligning reads from RNA sequencing experiments. HISAT uses an indexing scheme based on the Burrows-Wheeler transform and the Ferragina-Manzini (FM) index, employing two types of indexes for alignment: a whole-genome FM index to anchor each alignment and numerous local FM indexes for very rapid extensions of these alignments. HISAT's hierarchical index for the human genome contains 48,000 local FM indexes, each representing a genomic region of ∼64,000 bp. Tests on real and simulated data sets showed that HISAT is the fastest system currently available, with equal or better accuracy than any other method. Despite its large number of indexes, HISAT requires only 4.3 gigabytes of memory. HISAT supports genomes of any size, including those larger than 4 billion bases.
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                Author and article information

                Contributors
                Journal
                Protein Cell
                Protein Cell
                proteincell
                Protein & Cell
                Oxford University Press (US )
                1674-800X
                1674-8018
                June 2023
                30 November 2022
                30 November 2022
                : 14
                : 6
                : 398-415
                Affiliations
                Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China
                Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University , Beijing 100053, China
                State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China
                Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China
                Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University , Beijing 100053, China
                Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China
                Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University , Beijing 100053, China
                State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                Altos Labs, Inc., San Diego , CA 94022, USA
                Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China
                Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University , Beijing 100053, China
                The Fifth People’s Hospital of Chongqing , Chongqing 400062, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation , Beijing 100101, China
                Sino-Danish College, University of Chinese Academy of Sciences , Beijing 101408, China
                Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053, China
                Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuan Wu Hospital, Capital Medical University , Beijing 100053, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101, China
                Author notes
                Correspondence: wangsi@ 123456xwh.ccmu.edu.cn (S. Wang)

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0003-2431-0612
                https://orcid.org/0000-0002-8885-5104
                https://orcid.org/0000-0001-9289-8177
                https://orcid.org/0000-0002-3988-5067
                Article
                pwac062
                10.1093/procel/pwac062
                10246722
                37285263
                0730897f-bc89-4589-9736-11a2a359387f
                ©The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 August 2022
                : 16 October 2022
                : 03 February 2023
                Page count
                Pages: 18
                Funding
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2020YFA0804000
                Funded by: Strategic Priority Research Program of the Chinese Academy of Sciences;
                Award ID: XDA16000000
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 82001477
                Award ID: 81921006
                Award ID: 82125011
                Award ID: 92149301
                Award ID: 92168201
                Award ID: 91949209
                Award ID: 92049304
                Award ID: 92049116
                Award ID: 32121001
                Award ID: 32171447, 82192863
                Award ID: 82122024
                Award ID: 82071588
                Award ID: 32000500
                Award ID: 81861168034
                Award ID: 82271600
                Award ID: 82201727
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2018YFC2000100
                Award ID: 2018YFA0107203
                Award ID: 2020YFA0112200
                Award ID: 2021YFF1201005
                Award ID: 2021ZD0202401, 2022YFA1103700
                Award ID: 2021YFA1101401
                Funded by: Young Scientists in Basic Research;
                Award ID: YSBR-076
                Award ID: YSBR-012
                Funded by: Program of the Beijing Natural Science Foundation;
                Award ID: Z190019
                Funded by: K. C. Wong Education Foundation, DOI 10.13039/501100012692;
                Award ID: GJTD-2019-06
                Award ID: GJTD-2019-08
                Funded by: Tencent Foundation;
                Award ID: 2021-1045
                Funded by: The Pilot Project for Public Welfare Development;
                Funded by: Reform of Beijing-affiliated Medical Research Institutes;
                Award ID: 11000022T000000461062
                Funded by: Youth Innovation Promotion Association of CAS;
                Award ID: E1CAZW0401
                Award ID: 2022083
                Funded by: Young Elite Scientists Sponsorship Program by CAST;
                Award ID: YESS20200012
                Award ID: YESS20210002
                Funded by: Informatization Plan of Chinese Academy of Sciences;
                Award ID: CAS-WX2021SF-0301
                Award ID: CAS-WX2022SDC-XK14
                Award ID: CAS-WX2021SF-0101
                Funded by: Beijing Hospitals Authority Youth Programme;
                Award ID: QML20200802
                Funded by: Open Research Program of State Key Laboratory of Membrane Biology;
                Award ID: 2021KF02
                Funded by: Key Laboratory of Stem Cells and Tissue Engineering;
                Categories
                Research Articles
                AcademicSubjects/SCI00960

                single-cell rna-sequencing,que,hair follicle regeneration,endothelial cells,hif-1α

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