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Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes.
Lendemeijer, Bas; Unkel, Maurits; Smeenk, Hilde; Mossink, Britt; Hijazi, Sara; Gordillo-Sampedro, Sara; Shpak, Guy; Slump, Denise E; van den Hout, Mirjam C G N; van IJcken, Wilfred F J; Bindels, Eric M J; Hoogendijk, Witte J G; Nadif Kasri, Nael; de Vrij, Femke M S; Kushner, Steven A.
Afiliação
  • Lendemeijer B; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Unkel M; Department of Psychiatry, Columbia University, New York, New York 10027.
  • Smeenk H; Stavros Niarchos Foundation (SNF) Center for Precision Psychiatry & Mental Health, Columbia University, New York, New York 10027.
  • Mossink B; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Hijazi S; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Gordillo-Sampedro S; Department of Human Genetics, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands.
  • Shpak G; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Slump DE; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • van den Hout MCGN; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • van IJcken WFJ; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Bindels EMJ; Department of Cell Biology, Center for Biomics, Erasmus University Medical Center, Rotterdam 3015AA, The Netherlands.
  • Hoogendijk WJG; Department of Cell Biology, Center for Biomics, Erasmus University Medical Center, Rotterdam 3015AA, The Netherlands.
  • Nadif Kasri N; Department of Hematology, Erasmus University Medical Center, Rotterdam 3015AA, The Netherlands.
  • de Vrij FMS; Department of Psychiatry, Erasmus University Medical Center, Rotterdam 3015 AA, The Netherlands.
  • Kushner SA; Department of Human Genetics, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands.
eNeuro ; 11(9)2024 Sep.
Article em En | MEDLINE | ID: mdl-39227152
ABSTRACT
Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± 0.44 min-1 (hPSC-derived), 2.86 ± 0.64 min-1 (rat); p = 0.19]. In comparison, we found increased spike frequency within network bursts of human neurons cocultured with hPSC-derived astrocytes [56.31 ± 8.56 Hz (hPSC-derived), 24.77 ± 4.04 Hz (rat); p < 0.01], and whole-cell patch-clamp recordings revealed an increase of postsynaptic currents [2.76 ± 0.39 Hz (hPSC-derived), 1.07 ± 0.14 Hz (rat); p < 0.001], consistent with a corresponding increase in synapse density [14.90 ± 1.27/100 µm2 (hPSC-derived), 8.39 ± 0.63/100 µm2 (rat); p < 0.001]. Taken together, we show that hPSC-derived astrocytes compare favorably with rat astrocytes in supporting human neural network activity and maturation, providing a fully human platform for investigating astrocyte function and neuronal-glial interactions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Técnicas de Cocultura / Células-Tronco Pluripotentes / Neurônios Limite: Animals / Humans Idioma: En Revista: ENeuro Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Técnicas de Cocultura / Células-Tronco Pluripotentes / Neurônios Limite: Animals / Humans Idioma: En Revista: ENeuro Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda País de publicação: Estados Unidos