ORCID Profile
0000-0002-4539-1776
Current Organisation
Karolinska Institutet
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Publisher: Springer Science and Business Media LLC
Date: 12-05-2020
Publisher: Springer Science and Business Media LLC
Date: 25-06-2018
Publisher: Cold Spring Harbor Laboratory
Date: 17-09-2017
DOI: 10.1101/186445
Abstract: Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryogenesis in the central nervous system (CNS). It is unclear whether there is a correlation between these waves and different transcriptional oligodendrocyte (OL) states at adult stages. Here we present a bulk and single-cell transcriptomics resource providing insights on how transitions between these states occur. We show that E13.5 Pdgfra+ populations are not OPCs, exhibiting instead hallmarks of neural progenitors. A subset of these progenitors, which we refer as pre-OPCs, rewires their transcriptional landscape, converging into indistinguishable OPC states at E17.5 and post-natal stages. P7 brain and spinal cord OPCs present similar transcriptional profiles at the single-cell level, indicating that OPC states are not region-specific. Postnatal OPC progeny of E13.5 Pdgfra+ have electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves. In addition, lineage tracing indicates that a subset of E13.5 Pdgfra+ cells also originate cells of the pericyte lineage. In summary, our results indicate that embryonic Pdgfra+ cells are erse and give rise at post-natal stages to distinct cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions.
Publisher: Oxford University Press (OUP)
Date: 21-08-2014
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: Springer Science and Business Media LLC
Date: 04-12-2020
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.NBD.2012.08.006
Abstract: Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem rogenitor cells present in the human ventral midbrain (hVM) tissue. Our results show that hVM neurospheres (hVMN) with low cell numbers, unlike their rodent counterparts, expand the total number of cells 3-fold, whilst retaining their capacity to differentiate into midbrain DA neurons. Moreover, Wnt5a promoted DA differentiation of expanded cells resulting in improved morphological maturation, midbrain DA marker expression, DA release and electrophysiological properties. This method results in cell preparations that, after expansion and differentiation, can contain 6-fold more midbrain DA neurons than the starting VM preparation. Thus, our results provide evidence that by improving expansion and differentiation of progenitors present in the hVM it is possible to greatly enrich cell preparations for DA neurons. This method could substantially reduce the amount of human fetal midbrain tissue necessary for CRT in patients with PD, which could have major implications for the widespread adoption of this approach.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1038/S41593-020-00779-0
Abstract: A Correction to this paper has been published: 0.1038/s41593-020-00779-0.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2020
No related grants have been discovered for Jens Hjerling Leffler.