High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq
Neonatal hypoxic-ischemic encephalopathy (HIE) encompasses brain injuries resulting from dysregulated oxygen or blood flow to the brain before, during, or immediately after birth. During the acute phase, neuronal damage is driven by excitotoxicity, with permanent injury manifesting over the subseque...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240558082500113X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850246243590078464 |
|---|---|
| author | Nao Wakui Takashi Shimbo Morifumi Hanawa Tomomi Kitayama Yukari Yamamoto Yuya Ouchi Kotaro Saga Aiko Okada Kazuya Mimura Katsuto Tamai Masayuki Endo |
| author_facet | Nao Wakui Takashi Shimbo Morifumi Hanawa Tomomi Kitayama Yukari Yamamoto Yuya Ouchi Kotaro Saga Aiko Okada Kazuya Mimura Katsuto Tamai Masayuki Endo |
| author_sort | Nao Wakui |
| collection | DOAJ |
| description | Neonatal hypoxic-ischemic encephalopathy (HIE) encompasses brain injuries resulting from dysregulated oxygen or blood flow to the brain before, during, or immediately after birth. During the acute phase, neuronal damage is driven by excitotoxicity, with permanent injury manifesting over the subsequent hours. Treatment options have limited efficacy, requiring deeper insights into HIE pathogenesis. Recent advances in single-cell RNA sequencing have enabled molecular investigations of diverse diseases. However, the large size of certain cells, such as neurons, has posed challenges in studying conditions where neuronal damage is central. Thus, we employed single-nucleus RNA sequencing to evaluate damages in a mouse model of HIE and found pronounced changes in the hippocampus with significantly reduced neuronal populations. We observed the characteristic activation of hippocampal microglia, confirmed by immunostaining in the HIE model. These alterations were specific to combined hypoxic-ischemic conditions and were not observed with hypoxia or ischemia alone. These findings provide insights into the molecular and anatomical impact of HIE and highlight the hippocampus as a critical focus for understanding disease mechanisms and therapeutic development. |
| format | Article |
| id | doaj-art-7578b560ce26422b95b2d4235e8d779d |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-7578b560ce26422b95b2d4235e8d779d2025-08-20T01:59:14ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210202610.1016/j.bbrep.2025.102026High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seqNao Wakui0Takashi Shimbo1Morifumi Hanawa2Tomomi Kitayama3Yukari Yamamoto4Yuya Ouchi5Kotaro Saga6Aiko Okada7Kazuya Mimura8Katsuto Tamai9Masayuki Endo10Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; Corresponding author. StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Yamadaoka 2-8, Suita, Osaka, 565-0871, Japan.StemRIM Inc., Ibaraki, Osaka, JapanStemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, JapanStemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, JapanStemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan; StemRIM Inc., Ibaraki, Osaka, JapanDepartment of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, Japan; Department of Children's and Women's Health, Division of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanNeonatal hypoxic-ischemic encephalopathy (HIE) encompasses brain injuries resulting from dysregulated oxygen or blood flow to the brain before, during, or immediately after birth. During the acute phase, neuronal damage is driven by excitotoxicity, with permanent injury manifesting over the subsequent hours. Treatment options have limited efficacy, requiring deeper insights into HIE pathogenesis. Recent advances in single-cell RNA sequencing have enabled molecular investigations of diverse diseases. However, the large size of certain cells, such as neurons, has posed challenges in studying conditions where neuronal damage is central. Thus, we employed single-nucleus RNA sequencing to evaluate damages in a mouse model of HIE and found pronounced changes in the hippocampus with significantly reduced neuronal populations. We observed the characteristic activation of hippocampal microglia, confirmed by immunostaining in the HIE model. These alterations were specific to combined hypoxic-ischemic conditions and were not observed with hypoxia or ischemia alone. These findings provide insights into the molecular and anatomical impact of HIE and highlight the hippocampus as a critical focus for understanding disease mechanisms and therapeutic development.http://www.sciencedirect.com/science/article/pii/S240558082500113XNeonatal hypoxic-ischemic encephalopathyMouse modelSingle-nucleus RNA sequencingNeuronal damageHippocampusInterferon activation |
| spellingShingle | Nao Wakui Takashi Shimbo Morifumi Hanawa Tomomi Kitayama Yukari Yamamoto Yuya Ouchi Kotaro Saga Aiko Okada Kazuya Mimura Katsuto Tamai Masayuki Endo High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq Biochemistry and Biophysics Reports Neonatal hypoxic-ischemic encephalopathy Mouse model Single-nucleus RNA sequencing Neuronal damage Hippocampus Interferon activation |
| title | High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq |
| title_full | High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq |
| title_fullStr | High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq |
| title_full_unstemmed | High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq |
| title_short | High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq |
| title_sort | high resolution transcriptome analysis on a mouse model of neonatal hypoxic ischemic encephalopathy using single nucleus rna seq |
| topic | Neonatal hypoxic-ischemic encephalopathy Mouse model Single-nucleus RNA sequencing Neuronal damage Hippocampus Interferon activation |
| url | http://www.sciencedirect.com/science/article/pii/S240558082500113X |
| work_keys_str_mv | AT naowakui highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT takashishimbo highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT morifumihanawa highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT tomomikitayama highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT yukariyamamoto highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT yuyaouchi highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT kotarosaga highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT aikookada highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT kazuyamimura highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT katsutotamai highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq AT masayukiendo highresolutiontranscriptomeanalysisonamousemodelofneonatalhypoxicischemicencephalopathyusingsinglenucleusrnaseq |