Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases
Induced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patient...
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MDPI AG
2018-05-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/7/5/38 |
| _version_ | 1797726673019338752 |
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| author | Bor Luen Tang |
| author_facet | Bor Luen Tang |
| author_sort | Bor Luen Tang |
| collection | DOAJ |
| description | Induced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patients, which may offer insights into disease etiology that are otherwise unobtainable with available animal or human proxies. There are two good recent examples of such important insights with diseased neurons derived via either the iPSC or iN approaches. In one, induced motor neurons (iMNs) derived from iPSCs of Amyotrophic lateral sclerosis/Frontotemporal dementia (ALS/FTD) patients with a C9orf72 repeat expansion revealed a haploinsufficiency of protein function resulting from the intronic expansion and deficiencies in motor neuron vesicular trafficking and lysosomal biogenesis that were not previously obvious in knockout mouse models. In another, striatal medium spinal neurons (MSNs) derived directly from fibroblasts of Huntington’s disease (HD) patients recapitulated age-associated disease signatures of mutant Huntingtin (mHTT) aggregation and neurodegeneration that were not prominent in neurons differentiated indirectly via iPSCs from HD patients. These results attest to the tremendous potential for pathologically accurate and mechanistically revealing disease modelling with advances in the derivation of iPSCs and iNs. |
| first_indexed | 2024-03-12T10:48:59Z |
| format | Article |
| id | doaj.art-da7dc6e4dde64205998d42c398f563f4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:48:59Z |
| publishDate | 2018-05-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-da7dc6e4dde64205998d42c398f563f42023-09-02T07:18:21ZengMDPI AGCells2073-44092018-05-01753810.3390/cells7050038cells7050038Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative DiseasesBor Luen Tang0Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeInduced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patients, which may offer insights into disease etiology that are otherwise unobtainable with available animal or human proxies. There are two good recent examples of such important insights with diseased neurons derived via either the iPSC or iN approaches. In one, induced motor neurons (iMNs) derived from iPSCs of Amyotrophic lateral sclerosis/Frontotemporal dementia (ALS/FTD) patients with a C9orf72 repeat expansion revealed a haploinsufficiency of protein function resulting from the intronic expansion and deficiencies in motor neuron vesicular trafficking and lysosomal biogenesis that were not previously obvious in knockout mouse models. In another, striatal medium spinal neurons (MSNs) derived directly from fibroblasts of Huntington’s disease (HD) patients recapitulated age-associated disease signatures of mutant Huntingtin (mHTT) aggregation and neurodegeneration that were not prominent in neurons differentiated indirectly via iPSCs from HD patients. These results attest to the tremendous potential for pathologically accurate and mechanistically revealing disease modelling with advances in the derivation of iPSCs and iNs.http://www.mdpi.com/2073-4409/7/5/38induced pluripotent stem cells (iPSCs)induced neuronal (iN) cellsC9ORF72Huntingtinamyotrophic lateral sclerosis (ALS)Huntington’s diseaseneurodegenerative diseases |
| spellingShingle | Bor Luen Tang Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases Cells induced pluripotent stem cells (iPSCs) induced neuronal (iN) cells C9ORF72 Huntingtin amyotrophic lateral sclerosis (ALS) Huntington’s disease neurodegenerative diseases |
| title | Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases |
| title_full | Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases |
| title_fullStr | Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases |
| title_full_unstemmed | Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases |
| title_short | Patient-Derived iPSCs and iNs—Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases |
| title_sort | patient derived ipscs and ins shedding new light on the cellular etiology of neurodegenerative diseases |
| topic | induced pluripotent stem cells (iPSCs) induced neuronal (iN) cells C9ORF72 Huntingtin amyotrophic lateral sclerosis (ALS) Huntington’s disease neurodegenerative diseases |
| url | http://www.mdpi.com/2073-4409/7/5/38 |
| work_keys_str_mv | AT borluentang patientderivedipscsandinssheddingnewlightonthecellularetiologyofneurodegenerativediseases |