An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration
Abstract Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Zoological Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40851-022-00190-6 |
| _version_ | 1811289209415139328 |
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| author | Akira Satoh Rena Kashimoto Ayaka Ohashi Saya Furukawa Sakiya Yamamoto Takeshi Inoue Toshinori Hayashi Kiyokazu Agata |
| author_facet | Akira Satoh Rena Kashimoto Ayaka Ohashi Saya Furukawa Sakiya Yamamoto Takeshi Inoue Toshinori Hayashi Kiyokazu Agata |
| author_sort | Akira Satoh |
| collection | DOAJ |
| description | Abstract Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2FF treatment can induce dermis-derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis-derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. To clarify the factors that can provide the plasticity in differentiation, we performed the interspecies comparative analysis between newt cells and mouse cells and found the Pde4b gene was upregulated by B2FF treatment only in the newt cells. Blocking PDE4B signaling by a chemical PDE4 inhibitor suppressed dermis-to-cartilage transformation and the mosaic knockout animals showed consistent results. Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration. |
| first_indexed | 2024-04-13T03:50:53Z |
| format | Article |
| id | doaj.art-1f708a5b800a43229a77fb8d42c2b5a2 |
| institution | Directory Open Access Journal |
| issn | 2056-306X |
| language | English |
| last_indexed | 2024-04-13T03:50:53Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Zoological Letters |
| spelling | doaj.art-1f708a5b800a43229a77fb8d42c2b5a22022-12-22T03:03:49ZengBMCZoological Letters2056-306X2022-04-018111710.1186/s40851-022-00190-6An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regenerationAkira Satoh0Rena Kashimoto1Ayaka Ohashi2Saya Furukawa3Sakiya Yamamoto4Takeshi Inoue5Toshinori Hayashi6Kiyokazu Agata7Research Core for Interdisciplinary Sciences (RCIS), Okayama UniversityGraduate School of Environmental and Life Science, Okayama UniversityGraduate School of Environmental and Life Science, Okayama UniversityFaculty of Science, Department of Biological Sciences, Okayama UniversityFaculty of Science, Department of Biological Sciences, Okayama UniversityDivision of Adaptation Physiology, Faculty of Medicine, Tottori UniversityAmphibian Research Center, Hiroshima UniversityLaboratory of Regeneration Biology, National Institute for Basic BiologyAbstract Urodele amphibians, Pleurodeles waltl and Ambystoma mexicanum, have organ-level regeneration capability, such as limb regeneration. Multipotent cells are induced by an endogenous mechanism in amphibian limb regeneration. It is well known that dermal fibroblasts receive regenerative signals and turn into multipotent cells, called blastema cells. However, the induction mechanism of the blastema cells from matured dermal cells was unknown. We previously found that BMP2, FGF2, and FGF8 (B2FF) could play sufficient roles in blastema induction in urodele amphibians. Here, we show that B2FF treatment can induce dermis-derived cells that can participate in multiple cell lineage in limb regeneration. We first established a newt dermis-derived cell line and confirmed that B2FF treatment on the newt cells provided plasticity in cellular differentiation in limb regeneration. To clarify the factors that can provide the plasticity in differentiation, we performed the interspecies comparative analysis between newt cells and mouse cells and found the Pde4b gene was upregulated by B2FF treatment only in the newt cells. Blocking PDE4B signaling by a chemical PDE4 inhibitor suppressed dermis-to-cartilage transformation and the mosaic knockout animals showed consistent results. Our results are a valuable insight into how dermal fibroblasts acquire multipotency during the early phase of limb regeneration via an endogenous program in amphibian limb regeneration.https://doi.org/10.1186/s40851-022-00190-6Pde4bLimb regenerationPleurodels waltlAmbystoma mexicanumDedifferentiationReprogramming |
| spellingShingle | Akira Satoh Rena Kashimoto Ayaka Ohashi Saya Furukawa Sakiya Yamamoto Takeshi Inoue Toshinori Hayashi Kiyokazu Agata An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration Zoological Letters Pde4b Limb regeneration Pleurodels waltl Ambystoma mexicanum Dedifferentiation Reprogramming |
| title | An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| title_full | An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| title_fullStr | An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| title_full_unstemmed | An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| title_short | An approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| title_sort | approach for elucidating dermal fibroblast dedifferentiation in amphibian limb regeneration |
| topic | Pde4b Limb regeneration Pleurodels waltl Ambystoma mexicanum Dedifferentiation Reprogramming |
| url | https://doi.org/10.1186/s40851-022-00190-6 |
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