Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing
Summary: Keratinocyte differentiation is an intricate process that is regulated by multiple mediators. Using cultured human keratinocytes, we found that lysophosphatidic acid (LPA) induced the differentiation of a previously unsuspected keratinocyte subpopulation expressing the extracellular matrix...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422200400X |
| _version_ | 1818644870850412544 |
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| author | Ratklao Siriwach Anh Quynh Ngo Makio Higuchi Kentaro Arima Satoko Sakamoto Akira Watanabe Shuh Narumiya Dean Thumkeo |
| author_facet | Ratklao Siriwach Anh Quynh Ngo Makio Higuchi Kentaro Arima Satoko Sakamoto Akira Watanabe Shuh Narumiya Dean Thumkeo |
| author_sort | Ratklao Siriwach |
| collection | DOAJ |
| description | Summary: Keratinocyte differentiation is an intricate process that is regulated by multiple mediators. Using cultured human keratinocytes, we found that lysophosphatidic acid (LPA) induced the differentiation of a previously unsuspected keratinocyte subpopulation expressing the extracellular matrix protein, thrombospondin-1 (THBS1). This action of LPA was mediated by the RHO/ROCK-SRF signaling downstream of LPA1 and LPA5 receptors and required ERK activity. Suppression of THBS1 in vitro suggested a migratory role of THBS1+ keratinocytes. Moreover, we analyzed publicly deposited single-cell RNA sequencing dataset and identified Thbs1-expressing keratinocytes in the mouse wound skin. Immunohistochemistry analysis revealed that Thbs1+ keratinocytes were apparently differentiated from basal keratinocytes upon wounding, subsequently polarized and migrated suprabasally toward the wound front, and eventually underwent terminal differentiation in the neo-epidermis. Importantly, inhibition of Erk activity suppressed Thbs1+ keratinocyte differentiation in wound healing. Based on these findings, we suggest that THBS1+ keratinocyte is a migratory keratinocyte subpopulation that facilitates epidermal wound healing. |
| first_indexed | 2024-12-17T00:21:43Z |
| format | Article |
| id | doaj.art-97cf8e5bf9d5453188f35d32b6dbfe81 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T00:21:43Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-97cf8e5bf9d5453188f35d32b6dbfe812022-12-21T22:10:33ZengElsevieriScience2589-00422022-04-01254104130Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healingRatklao Siriwach0Anh Quynh Ngo1Makio Higuchi2Kentaro Arima3Satoko Sakamoto4Akira Watanabe5Shuh Narumiya6Dean Thumkeo7Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanMedical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanMedical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanDepartment of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Corresponding authorDepartment of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Corresponding authorSummary: Keratinocyte differentiation is an intricate process that is regulated by multiple mediators. Using cultured human keratinocytes, we found that lysophosphatidic acid (LPA) induced the differentiation of a previously unsuspected keratinocyte subpopulation expressing the extracellular matrix protein, thrombospondin-1 (THBS1). This action of LPA was mediated by the RHO/ROCK-SRF signaling downstream of LPA1 and LPA5 receptors and required ERK activity. Suppression of THBS1 in vitro suggested a migratory role of THBS1+ keratinocytes. Moreover, we analyzed publicly deposited single-cell RNA sequencing dataset and identified Thbs1-expressing keratinocytes in the mouse wound skin. Immunohistochemistry analysis revealed that Thbs1+ keratinocytes were apparently differentiated from basal keratinocytes upon wounding, subsequently polarized and migrated suprabasally toward the wound front, and eventually underwent terminal differentiation in the neo-epidermis. Importantly, inhibition of Erk activity suppressed Thbs1+ keratinocyte differentiation in wound healing. Based on these findings, we suggest that THBS1+ keratinocyte is a migratory keratinocyte subpopulation that facilitates epidermal wound healing.http://www.sciencedirect.com/science/article/pii/S258900422200400XBiological sciencesCell biologyStem cells research |
| spellingShingle | Ratklao Siriwach Anh Quynh Ngo Makio Higuchi Kentaro Arima Satoko Sakamoto Akira Watanabe Shuh Narumiya Dean Thumkeo Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing iScience Biological sciences Cell biology Stem cells research |
| title | Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing |
| title_full | Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing |
| title_fullStr | Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing |
| title_full_unstemmed | Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing |
| title_short | Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing |
| title_sort | single cell rna sequencing identifies a migratory keratinocyte subpopulation expressing thbs1 in epidermal wound healing |
| topic | Biological sciences Cell biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S258900422200400X |
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