dc.contributor.author |
McCaughey-Chapman, Amy |
|
dc.contributor.author |
Tarczyluk-Wells, Marta |
|
dc.contributor.author |
Combrinck, Catharina |
|
dc.contributor.author |
Edwards, Nicole |
|
dc.contributor.author |
Jones, Kathryn |
|
dc.contributor.author |
Connor, Bronwen |
|
dc.coverage.spatial |
Switzerland |
|
dc.date.accessioned |
2023-09-04T03:45:50Z |
|
dc.date.available |
2023-09-04T03:45:50Z |
|
dc.date.issued |
2023-01 |
|
dc.identifier.citation |
(2023). Frontiers in Cellular Neuroscience, 17, 1003188-. |
|
dc.identifier.issn |
1662-5102 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/65535 |
|
dc.description.abstract |
<b>Introduction:</b> With the increase in aging populations around the world, the development of <i>in vitro</i> human cell models to study neurodegenerative disease is crucial. A major limitation in using induced pluripotent stem cell (hiPSC) technology to model diseases of aging is that reprogramming fibroblasts to a pluripotent stem cell state erases age-associated features. The resulting cells show behaviors of an embryonic stage exhibiting longer telomeres, reduced oxidative stress, and mitochondrial rejuvenation, as well as epigenetic modifications, loss of abnormal nuclear morphologies, and age-associated features. <b>Methods:</b> We have developed a protocol utilizing stable, non-immunogenic chemically modified mRNA (cmRNA) to convert adult human dermal fibroblasts (HDFs) to human induced dorsal forebrain precursor (hiDFP) cells, which can subsequently be differentiated into cortical neurons. Analyzing an array of aging biomarkers, we demonstrate for the first time the effect of direct-to-hiDFP reprogramming on cellular age. <b>Results:</b> We confirm direct-to-hiDFP reprogramming does not affect telomere length or the expression of key aging markers. However, while direct-to-hiDFP reprogramming does not affect senescence-associated β-galactosidase activity, it enhances the level of mitochondrial reactive oxygen species and the amount of DNA methylation compared to HDFs. Interestingly, following neuronal differentiation of hiDFPs we observed an increase in cell soma size as well as neurite number, length, and branching with increasing donor age suggesting that neuronal morphology is altered with age. <b>Discussion:</b> We propose direct-to-hiDFP reprogramming provides a strategy for modeling age-associated neurodegenerative diseases allowing the persistence of age-associated signatures not seen in hiPSC-derived cultures, thereby facilitating our understanding of neurodegenerative disease and identification of therapeutic targets. |
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dc.format.medium |
Electronic-eCollection |
|
dc.language |
eng |
|
dc.publisher |
Frontiers |
|
dc.relation.ispartofseries |
Frontiers in cellular neuroscience |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
DNA methylation |
|
dc.subject |
direct cell reprogramming |
|
dc.subject |
human induced dorsal forebrain precursors |
|
dc.subject |
induced pluripotent stem cell |
|
dc.subject |
neurodegenerative disease |
|
dc.subject |
oxidative stress |
|
dc.subject |
senescence |
|
dc.subject |
telomere length |
|
dc.subject |
3206 Medical Biotechnology |
|
dc.subject |
3101 Biochemistry and Cell Biology |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
31 Biological Sciences |
|
dc.subject |
Stem Cell Research - Induced Pluripotent Stem Cell - Human |
|
dc.subject |
Stem Cell Research - Nonembryonic - Human |
|
dc.subject |
Regenerative Medicine |
|
dc.subject |
Aging |
|
dc.subject |
Stem Cell Research - Embryonic - Human |
|
dc.subject |
Neurosciences |
|
dc.subject |
Stem Cell Research - Induced Pluripotent Stem Cell |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
Stem Cell Research - Embryonic - Non-Human |
|
dc.subject |
Stem Cell Research |
|
dc.subject |
Genetics |
|
dc.subject |
Generic health relevance |
|
dc.subject |
Neurological |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Neurosciences & Neurology |
|
dc.subject |
PLURIPOTENT STEM-CELLS |
|
dc.subject |
NEURONS |
|
dc.subject |
DISEASE |
|
dc.subject |
0601 Biochemistry and Cell Biology |
|
dc.subject |
1109 Neurosciences |
|
dc.subject |
3209 Neurosciences |
|
dc.subject |
5202 Biological psychology |
|
dc.title |
Reprogramming of adult human dermal fibroblasts to induced dorsal forebrain precursor cells maintains aging signatures. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.3389/fncel.2023.1003188 |
|
pubs.begin-page |
1003188 |
|
pubs.volume |
17 |
|
dc.date.updated |
2023-08-24T00:38:17Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
36794263 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/36794263 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
951558 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Pharmacology |
|
dc.identifier.eissn |
1662-5102 |
|
pubs.number |
ARTN 1003188 |
|
pubs.record-created-at-source-date |
2023-08-24 |
|
pubs.online-publication-date |
2023-01-30 |
|