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  1. Article ; Online: Applying Multiomics to Basosquamous Carcinoma.

    Long, Gavin R / Kurdian, Arinnae I / Atwood, Scott X

    The Journal of investigative dermatology

    2024  

    Language English
    Publishing date 2024-02-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2023.11.026
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  2. Article ; Online: Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models.

    Atwood, Scott X / Plikus, Maksim V

    Experimental dermatology

    2021  Volume 30, Issue 3, Page(s) 298–303

    MeSH term(s) Hair Follicle ; Humans ; Models, Biological ; Organ Culture Techniques ; Organoids ; Skin/metabolism ; Skin Diseases/genetics ; Skin Physiological Phenomena
    Language English
    Publishing date 2021-02-10
    Publishing country Denmark
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1130936-2
    ISSN 1600-0625 ; 0906-6705
    ISSN (online) 1600-0625
    ISSN 0906-6705
    DOI 10.1111/exd.14296
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  3. Article ; Online: Defining the Genetics of Basosquamous Carcinoma.

    Tarapore, Eric / Atwood, Scott X

    The Journal of investigative dermatology

    2019  Volume 139, Issue 11, Page(s) 2258–2260

    Abstract: Basosquamous carcinoma (BSC) is a rare form of skin cancer with both basaloid and squamous morphology. Chiang et al. (2019) genetically define BSCs and demonstrate that BSCs likely originate as basal cell carcinomas that partially squamatize through ... ...

    Abstract Basosquamous carcinoma (BSC) is a rare form of skin cancer with both basaloid and squamous morphology. Chiang et al. (2019) genetically define BSCs and demonstrate that BSCs likely originate as basal cell carcinomas that partially squamatize through accumulation of ARID1A mutations and RAS/MAPK pathway activation.
    MeSH term(s) Adaptation, Physiological ; Carcinoma, Basal Cell ; Carcinoma, Basosquamous ; Humans ; Mutation ; Skin Neoplasms
    Language English
    Publishing date 2019-11-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2019.04.011
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  4. Article ; Online: ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1.

    Bardwell, A Jane / Wu, Beibei / Sarin, Kavita Y / Waterman, Marian L / Atwood, Scott X / Bardwell, Lee

    Life science alliance

    2022  Volume 5, Issue 11

    Abstract: Crosstalk between the Hedgehog and MAPK signaling pathways occurs in several types of cancer and contributes to clinical resistance to Hedgehog pathway inhibitors. Here we show that MAP kinase-mediated phosphorylation weakens the binding of the GLI1 ... ...

    Abstract Crosstalk between the Hedgehog and MAPK signaling pathways occurs in several types of cancer and contributes to clinical resistance to Hedgehog pathway inhibitors. Here we show that MAP kinase-mediated phosphorylation weakens the binding of the GLI1 transcription factor to its negative regulator SUFU. ERK2 phosphorylates GLI1 on three evolutionarily conserved target sites (S102, S116, and S130) located near the high-affinity binding site for SUFU; these phosphorylations cooperate to weaken the affinity of GLI1-SUFU binding by over 25-fold. Phosphorylation of any one, or even any two, of the three sites does not result in the level of SUFU release seen when all three sites are phosphorylated. Tumor-derived mutations in R100 and S105, residues bordering S102, also diminish SUFU binding, collectively defining a novel evolutionarily conserved SUFU affinity-modulating region. In cultured mammalian cells, GLI1 variants containing phosphomimetic substitutions of S102, S116, and S130 displayed an increased ability to drive transcription. We conclude that multisite phosphorylation of GLI1 by ERK2 or other MAP kinases weakens GLI1-SUFU binding, thereby facilitating GLI1 activation and contributing to both physiological and pathological crosstalk.
    MeSH term(s) Animals ; Binding Sites ; Cells, Cultured ; Conserved Sequence ; Hedgehog Proteins/metabolism ; Humans ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 1 ; Mutation ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phosphorylation ; Protein Binding ; Repressor Proteins ; Zinc Finger Protein GLI1/antagonists & inhibitors ; Zinc Finger Protein GLI1/genetics ; Zinc Finger Protein GLI1/metabolism
    Chemical Substances GLI1 protein, human ; Hedgehog Proteins ; Repressor Proteins ; SUFU protein, human ; Zinc Finger Protein GLI1 ; MAPK1 protein, human (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24)
    Language English
    Publishing date 2022-07-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202101353
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Screening cell-cell communication in spatial transcriptomics via collective optimal transport.

    Cang, Zixuan / Zhao, Yanxiang / Almet, Axel A / Stabell, Adam / Ramos, Raul / Plikus, Maksim V / Atwood, Scott X / Nie, Qing

    Nature methods

    2023  Volume 20, Issue 2, Page(s) 218–228

    Abstract: Spatial transcriptomic technologies and spatially annotated single-cell RNA sequencing datasets provide unprecedented opportunities to dissect cell-cell communication (CCC). However, incorporation of the spatial information and complex biochemical ... ...

    Abstract Spatial transcriptomic technologies and spatially annotated single-cell RNA sequencing datasets provide unprecedented opportunities to dissect cell-cell communication (CCC). However, incorporation of the spatial information and complex biochemical processes required in the reconstruction of CCC remains a major challenge. Here, we present COMMOT (COMMunication analysis by Optimal Transport) to infer CCC in spatial transcriptomics, which accounts for the competition between different ligand and receptor species as well as spatial distances between cells. A collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. Furthermore, we introduce downstream analysis tools to infer spatial signaling directionality and genes regulated by signaling using machine learning models. We apply COMMOT to simulation data and eight spatial datasets acquired with five different technologies to show its effectiveness and robustness in identifying spatial CCC in data with varying spatial resolutions and gene coverages. Finally, COMMOT identifies new CCCs during skin morphogenesis in a case study of human epidermal development.
    MeSH term(s) Humans ; Transcriptome ; Cell Communication/genetics ; Gene Expression Profiling ; Signal Transduction ; Computer Simulation ; Single-Cell Analysis
    Language English
    Publishing date 2023-01-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-022-01728-4
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  6. Article ; Online: sm"FISH"ing for Hedgehog.

    Drummond, Michael L / Atwood, Scott X

    The Journal of investigative dermatology

    2016  Volume 137, Issue 1, Page(s) 13–15

    Abstract: Patched (Ptch) receptors are critical negative regulators of Hedgehog signaling, where Ptch1 loss causes basal cell carcinoma and Ptch1;Ptch2 loss disrupts skin and hair follicle development. Adolphe et al. use single molecule fluorescent in situ ... ...

    Abstract Patched (Ptch) receptors are critical negative regulators of Hedgehog signaling, where Ptch1 loss causes basal cell carcinoma and Ptch1;Ptch2 loss disrupts skin and hair follicle development. Adolphe et al. use single molecule fluorescent in situ hybridization to show quantitatively that Ptch receptors create a Hedgehog signaling gradient that may specify hair follicle development.
    MeSH term(s) Animals ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Drug Resistance/genetics ; Hair Diseases/genetics ; Hair Diseases/pathology ; Hair Follicle/growth & development ; Hedgehog Proteins/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Patched Receptors/genetics ; Signal Transduction ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology
    Chemical Substances Hedgehog Proteins ; Patched Receptors
    Language English
    Publishing date 2016-12-22
    Publishing country United States
    Document type Journal Article ; Review ; Comment
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2016.07.021
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  7. Article ; Online: Illuminating Alternative Strategies to Treat Targeted Chemotherapy-Resistant Sporadic Basal Cell Carcinoma.

    Nguyen, Tuyen T L / Atwood, Scott X

    The Journal of investigative dermatology

    2018  Volume 138, Issue 5, Page(s) 1017–1019

    Abstract: Sporadic and basal cell nevus syndrome basal cell carcinomas show differential response rates to Smoothened inhibitors. Chiang et al. demonstrate notable decreases in UV-induced mutagenesis, total mutation load, genomic instability, and drug-resistant ... ...

    Abstract Sporadic and basal cell nevus syndrome basal cell carcinomas show differential response rates to Smoothened inhibitors. Chiang et al. demonstrate notable decreases in UV-induced mutagenesis, total mutation load, genomic instability, and drug-resistant mutations among basal cell nevus syndrome basal cell carcinomas using whole exome sequencing, which may explain the differences in drug response rates.
    MeSH term(s) Basal Cell Nevus Syndrome ; Carcinoma, Basal Cell ; Genomic Instability ; Humans ; Mutation ; Skin Neoplasms
    Language English
    Publishing date 2018-04-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2017.11.013
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  8. Article: Exploiting Endogenous Enzymes for Cancer-Cell Selective Metabolic Labeling of RNA in Vivo

    Beasley, Samantha / Vandewalle, Abigail / Singha, Monika / Nguyen, Kim / England, Whitney / Tarapore, Eric / Dai, Nan / Corrêa, Ivan R. / Atwood, Scott X. / Spitale, Robert C.

    Journal of the American Chemical Society. 2022 Apr. 13, v. 144, no. 16

    2022  

    Abstract: Tissues and organs are composed of many diverse cell types, making cell-specific gene expression profiling a major challenge. Herein we report that endogenous enzymes, unique to a cell of interest, can be utilized to enable cell-specific metabolic ... ...

    Abstract Tissues and organs are composed of many diverse cell types, making cell-specific gene expression profiling a major challenge. Herein we report that endogenous enzymes, unique to a cell of interest, can be utilized to enable cell-specific metabolic labeling of RNA. We demonstrate that appropriately designed “caged” nucleosides can be rendered active by serving as a substrate for cancer-cell specific enzymes to enable RNA metabolic labeling, only in cancer cells. We envision that the ease and high stringency of our approach will enable expression analysis of tumor cells in complex environments.
    Keywords RNA ; gene expression ; neoplasm cells ; neoplasms ; nucleosides
    Language English
    Dates of publication 2022-0413
    Size p. 7085-7088.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c02404
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury.

    Veniaminova, Natalia A / Jia, Yunlong Y / Hartigan, Adrien M / Huyge, Thomas J / Tsai, Shih-Ying / Grachtchouk, Marina / Nakagawa, Seitaro / Dlugosz, Andrzej A / Atwood, Scott X / Wong, Sunny Y

    Cell reports

    2023  Volume 42, Issue 9, Page(s) 113121

    Abstract: Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single- ... ...

    Abstract Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single-cell RNA sequencing, we uncovered both direct and indirect paths by which resident SG progenitors ordinarily differentiate into sebocytes, including transit through a Krt5+PPARγ+ transitional basal cell state. Upon skin injury, however, SG progenitors depart their niche, reepithelialize the wound, and are replaced by hair-follicle-derived stem cells. Furthermore, following targeted genetic ablation of >99% of SGs from dorsal skin, these glands unexpectedly regenerate within weeks. This regenerative process is mediated by alternative stem cells originating from the hair follicle bulge, is dependent upon FGFR2 signaling, and can be accelerated by inducing hair growth. Altogether, our studies demonstrate that stem cell plasticity promotes SG durability following injury.
    MeSH term(s) Sebaceous Glands ; Cell Differentiation ; Skin ; Hair Follicle ; Epithelial Cells
    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury.

    Veniaminova, Natalia A / Jia, Yunlong / Hartigan, Adrien M / Huyge, Thomas J / Tsai, Shih-Ying / Grachtchouk, Marina / Nakagawa, Seitaro / Dlugosz, Andrzej A / Atwood, Scott X / Wong, Sunny Y

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single ... ...

    Abstract Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single cell RNA-sequencing, we uncovered both direct and indirect paths by which these resident SG progenitors ordinarily differentiate into sebocytes, including transit through a PPARγ+Krt5+ transitional cell state. Upon skin injury, however, SG progenitors depart their niche, reepithelialize the wound, and are replaced by hair follicle-derived stem cells. Furthermore, following targeted genetic ablation of >99% of SGs from dorsal skin, these glands unexpectedly regenerate within weeks. This regenerative process is mediated by alternative stem cells originating from the hair follicle bulge, is dependent upon FGFR signaling, and can be accelerated by inducing hair growth. Altogether, our studies demonstrate that stem cell plasticity promotes SG durability following injury.
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.05.539454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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