Human 3D cellular model of hypoxic brain injury of prematurity
| العنوان: | Human 3D cellular model of hypoxic brain injury of prematurity |
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| المؤلفون: | Qihao Qi, Rebecca A. Krasnoff, Omer Revah, Hyun Woo Shin, A. Jeremy Willsey, Jin-Young Park, Theo D. Palmer, Sergiu P. Pașca, Ruth O'Hara, Anca M. Pașca |
| المصدر: | Nature medicine |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell type, Neurogenesis, Models, Neurological, Encephalopathy, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, medicine, Humans, Progenitor cell, Hypoxia, Brain, Cerebral Cortex, business.industry, Infant, Newborn, General Medicine, Human brain, Hypoxia (medical), medicine.disease, Cell Hypoxia, 3. Good health, Organoids, Corticogenesis, 030104 developmental biology, medicine.anatomical_structure, Cerebral cortex, Brain Injuries, Infant, Extremely Premature, 030220 oncology & carcinogenesis, Unfolded Protein Response, Unfolded protein response, medicine.symptom, T-Box Domain Proteins, business, Neuroscience |
| الوصف: | Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called encephalopathy of prematurity3. Over 80% of infants born before post-conception week 25 have moderate-to-severe long-term neurodevelopmental impairments4. The susceptible cell types in the cerebral cortex and the molecular mechanisms underlying associated gray-matter defects in premature infants remain unknown. Here we used human three-dimensional brain-region-specific organoids to study the effect of oxygen deprivation on corticogenesis. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and showed that these are related to the unfolded protein response and changes. Moreover, we verified these findings in human primary cortical tissue and demonstrated that a small-molecule modulator of the unfolded protein response pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be valuable for studying the environmental and genetic factors underlying injury in the developing human brain. |
| تدمد: | 1546-170X 1078-8956 |
| DOI: | 10.1038/s41591-019-0436-0 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2399164e43b6df8897f7b030c9e807ef https://doi.org/10.1038/s41591-019-0436-0 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2399164e43b6df8897f7b030c9e807ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 |
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| DOI: | 10.1038/s41591-019-0436-0 |