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Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain

Birtele, Marcella (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Storm, Petter (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Sharma, Yogita (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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Kajtez, Janko (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
Wahlestedt, Jenny Nelander (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
Sozzi, Edoardo (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Nilsson, Fredrik (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
Stott, Simon (author)
University of Cambridge
He, Xiaoling L (author)
University of Cambridge
Mattsson, Bengt (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Ottosson, Daniella Rylander (author)
Lund University,Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Regenerativ neurofysiologi,Forskargrupper vid Lunds universitet,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine,Regenerative Neurophysiology,Lund University Research Groups
Barker, Roger A (author)
University of Cambridge
Fiorenzano, Alessandro (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
Parmar, Malin (author)
Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Wallenberg Neurocentrum, Lund,Medicinska fakulteten,Developmental and Regenerative Neurobiology,Lund University Research Groups,Wallenberg Neuroscience Centre, Lund,Faculty of Medicine
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 (creator_code:org_t)
2022-12-08
2022
English.
In: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 149:23
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach revealed that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Publication and Content Type

art (subject category)
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