While the above‐mentioned astrocytes are found in all mammals, interlaminar and varicose projection astrocytes are higher‐order primate and human‐specific, respectively (Colombo, Gayol, Yanez, & Marco, 1997 Colombo, Lipina, Yanez, & Puissant, 1997 Falcone et al., 2019 Oberheim et al., 2009 Verkhratsky & Nedergaard, 2018). Multiple subtypes of astrocytes are distributed in different brain regions, including protoplasmic astrocytes in the gray matter, fibrous astrocytes in the white matter, velate astrocytes, perivascular astrocytes, Muller astrocytes, Bergman glia, and others (Verkhratsky & Nedergaard, 2018). However, most results were derived from rodent astrocytes, which have interspecies differences with human astrocytes (Hodge et al., 2019 Oberheim et al., 2009 Zhang et al., 2016) and the structural and functional properties of human astrocytes remain mainly unknown.Ĭompared with rodent counterparts, human astrocytes have specific genomic profiles, more extensive territories, more complex morphologies, faster intracellular Ca 2+ signal propagation, as well as primate‐specific morphologies (Oberheim et al., 2009 Oberheim, Wang, Goldman, & Nedergaard, 2006 Zhang et al., 2016). Cumulative evidence revealed that different morphologies and transcriptomes of astrocyte subtypes enriched in different brain regions contribute to the heterogeneity of astrocytic functions (Khakh & Deneen, 2019 Khakh & Sofroniew, 2015 Oberheim, Goldman, & Nedergaard, 2012). Astrocytes are tightly integrated into the neural circuits and regulate various aspects of CNS function, including modulation of neuronal development (Baldwin & Eroglu, 2017 Vainchtein et al., 2018 Van Horn & Ruthazer, 2018) and synaptic transmission (Krencik, van Asperen, & Ullian, 2017), regulation of ionic homeostasis (Olsen et al., 2015), recycling of neurotransmitters (Araque, Li, Doyle, & Haydon, 2000), regulation of metabolism and maintenance of the blood–brain barrier (Sofroniew & Vinters, 2010). This model provides a novel platform for understanding neuron‐glial interaction and its alterations in neurological diseases.Īstrocytes, a subtype of glial cells in the central nervous system, play an essential role in maintaining homeostasis of the Central Nervous System (CNS) (Verkhratsky & Nedergaard, 2018). Here we modeled human interlaminar astrocytes in humanized glial chimeric mice by engrafting astrocytes differentiated from human‐induced pluripotent stem cells into the mouse cortex. However, due to the lack of accessible experimental models, their functional properties and their role in regulating neuronal circuits remain unclear. These primate‐specific interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. In addition to the typical mammalian astrocyte architecture, the cerebral cortex of humans exhibits a radial distribution of interlaminar astrocytes in the supragranular layers. The heterogeneity of astrocyte populations underlies the diversity in their functions. Astrocytes, a highly heterogeneous population of glial cells, serve as essential regulators of brain development and homeostasis.
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