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Spatial RNA Sequenc...
Spatial RNA Sequencing Identifies Robust Markers of Vulnerable and Resistant Human Midbrain Dopamine Neurons and Their Expression in Parkinson's Disease
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Aguila, Julio (författare)
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Cheng, Shangli (författare)
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- Kee, Nigel (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Karolinska Institutet, Sweden
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Cao, Ming (författare)
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Wang, Menghan (författare)
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- Deng, Qiaolin (författare)
- Karolinska Institutet
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- Hedlund, Eva (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Karolinska Institutet, Sweden
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(creator_code:org_t)
- 2021-07-08
- 2021
- Engelska.
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 14
- Relaterad länk:
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https://doi.org/10.3...
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Defining transcriptional profiles of substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) dopamine neurons is critical to understanding their differential vulnerability in Parkinson's Disease (PD). Here, we determine transcriptomes of human SNc and VTA dopamine neurons using LCM-seq on a large sample cohort. We apply a bootstrapping strategy as sample input to DESeq2 and identify 33 stably differentially expressed genes (DEGs) between these two subpopulations. We also compute a minimal sample size for identification of stable DEGs, which highlights why previous reported profiles from small sample sizes display extensive variability. Network analysis reveal gene interactions unique to each subpopulation and highlight differences in regulation of mitochondrial stability, apoptosis, neuronal survival, cytoskeleton regulation, extracellular matrix modulation as well as synapse integrity, which could explain the relative resilience of VTA dopamine neurons. Analysis of PD tissues showed that while identified stable DEGs can distinguish the subpopulations also in disease, the SNc markers SLIT1 and ATP2A3 were down-regulated and thus appears to be biomarkers of disease. In summary, our study identifies human SNc and VTA marker profiles, which will be instrumental for studies aiming to modulate dopamine neuron resilience and to validate cell identity of stem cell-derived dopamine neurons.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- human midbrain dopamine neurons
- spatial transcriptomics
- laser microdissection
- RNA sequencing
- substantia nigra compacta
- ventral tegmental area
- Parkinson's disease
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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