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Single-Cell Profiling of Coding and Noncoding Genes in Human Dopamine Neuron Differentiation

Nilsson, Fredrik LU orcid ; Storm, Petter LU orcid ; Sozzi, Edoardo LU orcid ; Hidalgo Gil, David LU ; Birtele, Marcella LU orcid ; Sharma, Yogita LU ; Parmar, Malin LU orcid and Fiorenzano, Alessandro LU (2021) In Cells 10(1).
Abstract

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson's disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons... (More)

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson's disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cells
volume
10
issue
1
publisher
MDPI AG
external identifiers
  • scopus:85100083937
  • pmid:33445654
ISSN
2073-4409
DOI
10.3390/cells10010137
language
English
LU publication?
yes
id
7c907417-9758-4b5b-a48a-b55edea8eef8
date added to LUP
2021-02-15 16:37:20
date last changed
2024-06-13 07:04:26
@article{7c907417-9758-4b5b-a48a-b55edea8eef8,
  abstract     = {{<p>Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson's disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.</p>}},
  author       = {{Nilsson, Fredrik and Storm, Petter and Sozzi, Edoardo and Hidalgo Gil, David and Birtele, Marcella and Sharma, Yogita and Parmar, Malin and Fiorenzano, Alessandro}},
  issn         = {{2073-4409}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Single-Cell Profiling of Coding and Noncoding Genes in Human Dopamine Neuron Differentiation}},
  url          = {{https://lup.lub.lu.se/search/files/100827503/Nilsson_pdf_publication_in_cells.pdf}},
  doi          = {{10.3390/cells10010137}},
  volume       = {{10}},
  year         = {{2021}},
}