Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures
Abstract Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-023-00340-0 |
| _version_ | 1797453585437425664 |
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| author | Mingxing Lei Jingwei Jiang Mengyue Wang Wang Wu Jinwei Zhang Wanqian Liu Wei Zhou Yung-Chih Lai Ting-Xin Jiang Randall B. Widelitz Hans I-Chen Harn Li Yang Cheng-Ming Chuong |
| author_facet | Mingxing Lei Jingwei Jiang Mengyue Wang Wang Wu Jinwei Zhang Wanqian Liu Wei Zhou Yung-Chih Lai Ting-Xin Jiang Randall B. Widelitz Hans I-Chen Harn Li Yang Cheng-Ming Chuong |
| author_sort | Mingxing Lei |
| collection | DOAJ |
| description | Abstract Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane. Functionally, the spheroid becomes competent morphogenetic units (CMU) that promote regeneration of tissue patterns. The emergence of new cell types and molecular interactions during CMU formation was analyzed using scRNA-sequencing. Surprisingly, in newborn skin explants, IFNr signaling can induce apical-basal polarity in epidermal cell aggregates. Dermal-Tgfb induces basement membrane formation. Meanwhile, VEGF signaling mediates dermal cell attachment to the epidermal cyst shell, thus forming a CMU. Adult mouse and human fetal scalp cells fail to form a CMU but can be restored by adding IFNr or VEGF to achieve hair regeneration. We find different multi-cellular configurations and molecular pathways are used to achieve morphogenetic competence in developing skin, wound-induced hair neogenesis, and reconstituted explant cultures. Thus, multiple paths can be used to achieve tissue patterning. These insights encourage more studies of “in vitro morphogenesis” which may provide novel strategies to enhance regeneration. |
| first_indexed | 2024-03-09T15:24:56Z |
| format | Article |
| id | doaj.art-00b1439c568944e2a6108f3a7d4738f0 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-03-09T15:24:56Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-00b1439c568944e2a6108f3a7d4738f02023-11-26T12:33:58ZengNature Portfolionpj Regenerative Medicine2057-39952023-11-018111710.1038/s41536-023-00340-0Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant culturesMingxing Lei0Jingwei Jiang1Mengyue Wang2Wang Wu3Jinwei Zhang4Wanqian Liu5Wei Zhou6Yung-Chih Lai7Ting-Xin Jiang8Randall B. Widelitz9Hans I-Chen Harn10Li Yang11Cheng-Ming Chuong12Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalIntegrative Stem Cell Center, China Medical University HospitalDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaKey Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of BioengineeringDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaAbstract Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane. Functionally, the spheroid becomes competent morphogenetic units (CMU) that promote regeneration of tissue patterns. The emergence of new cell types and molecular interactions during CMU formation was analyzed using scRNA-sequencing. Surprisingly, in newborn skin explants, IFNr signaling can induce apical-basal polarity in epidermal cell aggregates. Dermal-Tgfb induces basement membrane formation. Meanwhile, VEGF signaling mediates dermal cell attachment to the epidermal cyst shell, thus forming a CMU. Adult mouse and human fetal scalp cells fail to form a CMU but can be restored by adding IFNr or VEGF to achieve hair regeneration. We find different multi-cellular configurations and molecular pathways are used to achieve morphogenetic competence in developing skin, wound-induced hair neogenesis, and reconstituted explant cultures. Thus, multiple paths can be used to achieve tissue patterning. These insights encourage more studies of “in vitro morphogenesis” which may provide novel strategies to enhance regeneration.https://doi.org/10.1038/s41536-023-00340-0 |
| spellingShingle | Mingxing Lei Jingwei Jiang Mengyue Wang Wang Wu Jinwei Zhang Wanqian Liu Wei Zhou Yung-Chih Lai Ting-Xin Jiang Randall B. Widelitz Hans I-Chen Harn Li Yang Cheng-Ming Chuong Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures npj Regenerative Medicine |
| title | Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| title_full | Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| title_fullStr | Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| title_full_unstemmed | Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| title_short | Epidermal–dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| title_sort | epidermal dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures |
| url | https://doi.org/10.1038/s41536-023-00340-0 |
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