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Front Cell Dev Biol. 2018 Feb 6;6:5. doi: 10.3389/fcell.2018.00005. eCollection 2018.

Central and Peripheral Nervous System Progenitors Derived from Human Pluripotent Stem Cells Reveal a Unique Temporal and Cell-Type Specific Expression of PMCAs.

Chen M1,2, Laursen SH1,2, Habekost M1,2, Knudsen CH1,2, Buchholdt SH1,2, Huang J3,4, Xu F3,4,5,6, Liu X3,5, Bolund L2,3,4,5, Luo Y2,3,4,5, Nissen P1,7, Febbraro F1,8, Denham M1,2.

Author information

1
Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, Denmark.
2
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
3
Beijing Genomics Institute, Shenzhen, China.
4
Lars Bolund Institute of Regenerative Medicine, Beijing Genomics Institute-Qingdao, Qingdao, China.
5
China National GeneBank, Beijing Genomics Institute, Shenzhen, China.
6
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
7
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
8
Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

Abstract

The P-type ATPases family consists of ion and lipid transporters. Their unique diversity in function and expression is critical for normal development. In this study we investigated human pluripotent stem cells (hPSC) and different neural progenitor states to characterize the expression of the plasma membrane calcium ATPases (PMCAs) during human neural development and in mature mesencephalic dopaminergic (mesDA) neurons. Our RNA sequencing data identified a dynamic change in ATPase expression correlating with the differentiation time of the neural progenitors, which was independent of the neuronal progenitor type. Expression of ATP2B1 and ATP2B4 were the most abundantly expressed, in accordance with their main role in Ca2+ regulation and we observed all of the PMCAs to have a subcellular punctate localization. Interestingly in hPSCs ATP2B1 and ATP2B3 were highly expressed in a cell cycle specific manner and ATP2B2 and ATP2B4 were highly expressed in a hPSC sub-population. In neural rosettes a strong apical PMCA expression was identified in the luminal region. Lastly, we confirmed all PMCAs to be expressed in mesDA neurons, however at varying levels. Our results reveal that PMCA expression dynamically changes during stem cell differentiation and highlights the diverging needs of cell populations to regulate and properly integrate Ca2+ changes, which can ultimately correspond to changes in specific stem cell transcription states.

KEYWORDS:

human pluripotent stem cells; mesencephalic dopaminergic neurons; neural stem cells; neuromesodermal progenitors; plasma membrane calcium ATPase

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