File Download

There are no files associated with this item.

Conference Paper: Elucidating the role of DLC1 Isoform 1 in Human Motor Neuron Development and Spinal Muscular Atrophy

TitleElucidating the role of DLC1 Isoform 1 in Human Motor Neuron Development and Spinal Muscular Atrophy
Authors
Issue Date2021
Citation
The virtual 2021 NYSCF Conference How to Cite?
AbstractSpinal muscular atrophy (SMA) is a motor neuron (MN) disease caused by loss of the ubiquitously expressed Survival Motor Neuron (SMN) spliceosome protein, resulting in selective degeneration of spinal MNs but the mechanisms underlying the specific loss of MNs remain unknown. A previous report showed that Deleted in Liver Cancer 1 (DLC1) is the most down-regulated gene in MNs derived from a SMA patient but its roles in MN development and SMA pathogenesis remain to be elucidated. Here, we detected a gradually increasing of DLC1-i1 expression level as human embryonic stem cells differentiated into MN lineage. Knockdown (KD) of DLC1-i1 led to a reduction in MN formation, axonal outgrowth and increase apoptosis, whereas overexpression of DLC1-i1 promoted MN differentiation with extensive axonal outgrowth. Importantly, SMN KD not only caused MN loss but also intron retention of DLC1-i1, resulting in downregulation of DLC1-i1 expression. We also confirmed decreased levels of DLC1-i1 in MNs derived from SMA patients’ urine derived induced pluripotent stem cells compared to healthy individuals. Altogether, our results indicate that DLC1-i1 plays an important role in MN differentiation and deficiency of SMN causes selective loss of MNs partly through disruption of DLC1-i1 splicing.
Persistent Identifierhttp://hdl.handle.net/10722/319125

 

DC FieldValueLanguage
dc.contributor.authorSHI, T-
dc.contributor.authorLiu, AJ-
dc.contributor.authorChan, HSS-
dc.contributor.authorCheung, MCH-
dc.date.accessioned2022-10-14T05:07:34Z-
dc.date.available2022-10-14T05:07:34Z-
dc.date.issued2021-
dc.identifier.citationThe virtual 2021 NYSCF Conference-
dc.identifier.urihttp://hdl.handle.net/10722/319125-
dc.description.abstractSpinal muscular atrophy (SMA) is a motor neuron (MN) disease caused by loss of the ubiquitously expressed Survival Motor Neuron (SMN) spliceosome protein, resulting in selective degeneration of spinal MNs but the mechanisms underlying the specific loss of MNs remain unknown. A previous report showed that Deleted in Liver Cancer 1 (DLC1) is the most down-regulated gene in MNs derived from a SMA patient but its roles in MN development and SMA pathogenesis remain to be elucidated. Here, we detected a gradually increasing of DLC1-i1 expression level as human embryonic stem cells differentiated into MN lineage. Knockdown (KD) of DLC1-i1 led to a reduction in MN formation, axonal outgrowth and increase apoptosis, whereas overexpression of DLC1-i1 promoted MN differentiation with extensive axonal outgrowth. Importantly, SMN KD not only caused MN loss but also intron retention of DLC1-i1, resulting in downregulation of DLC1-i1 expression. We also confirmed decreased levels of DLC1-i1 in MNs derived from SMA patients’ urine derived induced pluripotent stem cells compared to healthy individuals. Altogether, our results indicate that DLC1-i1 plays an important role in MN differentiation and deficiency of SMN causes selective loss of MNs partly through disruption of DLC1-i1 splicing.-
dc.languageeng-
dc.relation.ispartofThe virtual 2021 NYSCF Conference-
dc.titleElucidating the role of DLC1 Isoform 1 in Human Motor Neuron Development and Spinal Muscular Atrophy-
dc.typeConference_Paper-
dc.identifier.emailChan, HSS: sophehs@hku.hk-
dc.identifier.emailCheung, MCH: mcheung9@hku.hk-
dc.identifier.authorityLiu, AJ=rp02546-
dc.identifier.authorityChan, HSS=rp02210-
dc.identifier.authorityCheung, MCH=rp00245-
dc.identifier.hkuros338819-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats