Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons
<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by the loss of motor neurons. We utilized single-cell transcriptomics to uncover dysfunctional pathways in degenerating motor neurons differentiated from SOD1 E100G ALS patient-derived induced pluripote...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , |
| Published: |
2021
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513515349344256 |
|---|---|
| author | Seema C. Namboori (11031624) |
| author2 | Patricia Thomas (3489989) Ryan Ames (3486263) Sophie Hawkins (18421377) Lawrence O. Garrett (18589426) Craig R.G. Willis (18589429) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| author2_role | author author author author author author author author |
| author_facet | Seema C. Namboori (11031624) Patricia Thomas (3489989) Ryan Ames (3486263) Sophie Hawkins (18421377) Lawrence O. Garrett (18589426) Craig R.G. Willis (18589429) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| author_role | author |
| dc.creator.none.fl_str_mv | Seema C. Namboori (11031624) Patricia Thomas (3489989) Ryan Ames (3486263) Sophie Hawkins (18421377) Lawrence O. Garrett (18589426) Craig R.G. Willis (18589429) Alessandro Rosa (470248) Lawrence W. Stanton (6707191) Akshay Bhinge (173004) |
| dc.date.none.fl_str_mv | 2021-12-14T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.stemcr.2021.10.010 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Single-cell_transcriptomics_identifies_master_regulators_of_neurodegeneration_in_SOD1_ALS_iPSC-derived_motor_neurons/25867666 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Neurosciences ALS iPSC SOD1 spinal MN single-cell RNA-seq networks TGFβ developmental pathways |
| dc.title.none.fl_str_mv | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by the loss of motor neurons. We utilized single-cell transcriptomics to uncover dysfunctional pathways in degenerating motor neurons differentiated from SOD1 E100G ALS patient-derived induced pluripotent stem cells (iPSCs) and respective isogenic controls. Differential gene expression and network analysis identified activation of developmental pathways and core transcriptional factors driving the ALS motor neuron gene dysregulation. Specifically, we identified activation of SMAD2, a downstream mediator of the transforming growth factor β (TGF-β) signaling pathway as a key driver of SOD1 iPSC-derived motor neuron degeneration. Importantly, our analysis indicates that activation of TGFβ signaling may be a common mechanism shared between SOD1, FUS, C9ORF72, VCP, and sporadic ALS motor neurons. Our results demonstrate the utility of single-cell transcriptomics in mapping disease-relevant gene regulatory networks driving neurodegeneration in ALS motor neurons. We find that ALS-associated mutant SOD1 targets transcriptional networks that perturb motor neuron homeostasis.</p><h2>Other Information</h2> <p> Published in: Stem Cell Reports<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.stemcr.2021.10.010" target="_blank">https://dx.doi.org/10.1016/j.stemcr.2021.10.010</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_c037ce33afce9323084e76019d89aacf |
| identifier_str_mv | 10.1016/j.stemcr.2021.10.010 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25867666 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neuronsSeema C. Namboori (11031624)Patricia Thomas (3489989)Ryan Ames (3486263)Sophie Hawkins (18421377)Lawrence O. Garrett (18589426)Craig R.G. Willis (18589429)Alessandro Rosa (470248)Lawrence W. Stanton (6707191)Akshay Bhinge (173004)Biological sciencesGeneticsBiomedical and clinical sciencesNeurosciencesALSiPSCSOD1spinal MNsingle-cell RNA-seqnetworksTGFβdevelopmental pathways<p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by the loss of motor neurons. We utilized single-cell transcriptomics to uncover dysfunctional pathways in degenerating motor neurons differentiated from SOD1 E100G ALS patient-derived induced pluripotent stem cells (iPSCs) and respective isogenic controls. Differential gene expression and network analysis identified activation of developmental pathways and core transcriptional factors driving the ALS motor neuron gene dysregulation. Specifically, we identified activation of SMAD2, a downstream mediator of the transforming growth factor β (TGF-β) signaling pathway as a key driver of SOD1 iPSC-derived motor neuron degeneration. Importantly, our analysis indicates that activation of TGFβ signaling may be a common mechanism shared between SOD1, FUS, C9ORF72, VCP, and sporadic ALS motor neurons. Our results demonstrate the utility of single-cell transcriptomics in mapping disease-relevant gene regulatory networks driving neurodegeneration in ALS motor neurons. We find that ALS-associated mutant SOD1 targets transcriptional networks that perturb motor neuron homeostasis.</p><h2>Other Information</h2> <p> Published in: Stem Cell Reports<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.stemcr.2021.10.010" target="_blank">https://dx.doi.org/10.1016/j.stemcr.2021.10.010</a></p>2021-12-14T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.stemcr.2021.10.010https://figshare.com/articles/journal_contribution/Single-cell_transcriptomics_identifies_master_regulators_of_neurodegeneration_in_SOD1_ALS_iPSC-derived_motor_neurons/25867666CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258676662021-12-14T03:00:00Z |
| spellingShingle | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons Seema C. Namboori (11031624) Biological sciences Genetics Biomedical and clinical sciences Neurosciences ALS iPSC SOD1 spinal MN single-cell RNA-seq networks TGFβ developmental pathways |
| status_str | publishedVersion |
| title | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| title_full | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| title_fullStr | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| title_full_unstemmed | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| title_short | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| title_sort | Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons |
| topic | Biological sciences Genetics Biomedical and clinical sciences Neurosciences ALS iPSC SOD1 spinal MN single-cell RNA-seq networks TGFβ developmental pathways |