Portal de Periódicos da CAPES

Specification of transplantable astroglial subtypes from human pluripotent stem cells

2011; Nature Portfolio; Volume: 29; Issue: 6 Linguagem: Inglês

10.1038/nbt.1877

1546-1696

Robert Krencik, Jason P. Weick, Yan Liu, Zhijian Zhang, Su‐Chun Zhang,

Pluripotent Stem Cells Research

Krencik et al. present a chemically defined system for differentiating human pluripotent stem cells to large numbers of immature astrocytes, which mature further after transplantation to the neonatal mouse brain. By applying regional patterning factors at the neuroepithelial stage, the authors also succeed in generating different astrocytes subtypes. Human pluripotent stem cells (hPSCs) have been differentiated efficiently to neuronal cell types. However, directed differentiation of hPSCs to astrocytes and astroglial subtypes remains elusive. In this study, hPSCs were directed to nearly uniform populations of immature astrocytes (>90% S100β+ and GFAP+) in large quantities. The immature human astrocytes exhibit similar gene expression patterns as primary astrocytes, display functional properties such as glutamate uptake and promotion of synaptogenesis, and become mature astrocytes by forming connections with blood vessels after transplantation into the mouse brain. Furthermore, hPSC-derived neuroepithelia, patterned to rostral-caudal and dorsal-ventral identities with the same morphogens used for neuronal subtype specification, generate immature astrocytes that express distinct homeodomain transcription factors and display phenotypic differences of different astroglial subtypes. These human astroglial progenitors and immature astrocytes will be useful for studying astrocytes in brain development and function, understanding the roles of astrocytes in disease processes and developing novel treatments for neurological disorders.