Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury
Abstract Background Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve ph...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-024-03657-9 |
| _version_ | 1797275592586952704 |
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| author | Zhiyuan Yin Lingling Ge Zhe Cha Hui Gao Luodan A Yuxiao Zeng Xiaona Huang Xuan Cheng Kai Yao Zui Tao Haiwei Xu |
| author_facet | Zhiyuan Yin Lingling Ge Zhe Cha Hui Gao Luodan A Yuxiao Zeng Xiaona Huang Xuan Cheng Kai Yao Zui Tao Haiwei Xu |
| author_sort | Zhiyuan Yin |
| collection | DOAJ |
| description | Abstract Background Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration. Methods A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI). The critical time point for the fate determination of MG gliosis was determined through immunohistochemical staining methods. Then, bulk-RNA and single-cell RNA seq techniques were used to elucidate the changes in RNA transcription of the retina and MG at that time point, and new genes that may determine the fate transition of MG were screened. Finally, the selected gene was specifically overexpressed in MG cells through adeno-associated viruses (AAV) in the mouse RP model. Bulk-RNA seq technique, immunohistochemical staining methods, and visual function testing were used to elucidate and validate the mechanism of new genes function on MG cell fate transition and retinal function. Results Here, we found the critical time point for MG gliosis fate determination was 3 days post SI injection. Hmga2 was screened out as a candidate regulator for the cell fate transition of MG. After retinal injury caused by SI, the Hmga2 protein is temporarily and lowly expressed in MG cells. Overexpression of Hmga2 in MG down-regulated glial cell related genes and up-regulated photoreceptor related genes. Besides, overexpressing Hmga2 exclusively to MG reduced MG gliosis, made MG obtain cone’s marker, and retained visual function in mice with acute retinal injury. Conclusion Our results suggested the unique reprogramming properties of Hmga2 in regulating the fate transition of MG and neuroprotective effects on the retina with acute injury. This work uncovers the reprogramming ability of epigenetic factors in MG. |
| first_indexed | 2024-03-07T15:16:41Z |
| format | Article |
| id | doaj.art-09469798c0364458b1578be744c202ed |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-07T15:16:41Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-09469798c0364458b1578be744c202ed2024-03-05T17:52:15ZengBMCStem Cell Research & Therapy1757-65122024-02-0115112010.1186/s13287-024-03657-9Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injuryZhiyuan Yin0Lingling Ge1Zhe Cha2Hui Gao3Luodan A4Yuxiao Zeng5Xiaona Huang6Xuan Cheng7Kai Yao8Zui Tao9Haiwei Xu10Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Institute of Visual Neuroscience and Stem Cell Engineering, College of Life Sciences and Health, Wuhan University of Science and TechnologySouthwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University)Abstract Background Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration. Methods A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI). The critical time point for the fate determination of MG gliosis was determined through immunohistochemical staining methods. Then, bulk-RNA and single-cell RNA seq techniques were used to elucidate the changes in RNA transcription of the retina and MG at that time point, and new genes that may determine the fate transition of MG were screened. Finally, the selected gene was specifically overexpressed in MG cells through adeno-associated viruses (AAV) in the mouse RP model. Bulk-RNA seq technique, immunohistochemical staining methods, and visual function testing were used to elucidate and validate the mechanism of new genes function on MG cell fate transition and retinal function. Results Here, we found the critical time point for MG gliosis fate determination was 3 days post SI injection. Hmga2 was screened out as a candidate regulator for the cell fate transition of MG. After retinal injury caused by SI, the Hmga2 protein is temporarily and lowly expressed in MG cells. Overexpression of Hmga2 in MG down-regulated glial cell related genes and up-regulated photoreceptor related genes. Besides, overexpressing Hmga2 exclusively to MG reduced MG gliosis, made MG obtain cone’s marker, and retained visual function in mice with acute retinal injury. Conclusion Our results suggested the unique reprogramming properties of Hmga2 in regulating the fate transition of MG and neuroprotective effects on the retina with acute injury. This work uncovers the reprogramming ability of epigenetic factors in MG.https://doi.org/10.1186/s13287-024-03657-9Hmga2Müller gliaGliosisReprogrammingEpigeneticProliferation |
| spellingShingle | Zhiyuan Yin Lingling Ge Zhe Cha Hui Gao Luodan A Yuxiao Zeng Xiaona Huang Xuan Cheng Kai Yao Zui Tao Haiwei Xu Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury Stem Cell Research & Therapy Hmga2 Müller glia Gliosis Reprogramming Epigenetic Proliferation |
| title | Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury |
| title_full | Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury |
| title_fullStr | Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury |
| title_full_unstemmed | Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury |
| title_short | Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury |
| title_sort | identifying hmga2 preserving visual function by promoting a shift of muller glia cell fate in mice with acute retinal injury |
| topic | Hmga2 Müller glia Gliosis Reprogramming Epigenetic Proliferation |
| url | https://doi.org/10.1186/s13287-024-03657-9 |
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