Cortical astrocytes develop in a plastic manner at both clonal and cellular levels

Abstract

Astrocytes play essential roles in the neural tissue where they form a continuous network, while displaying important local heterogeneity. Here, we performed multiclonal lineage tracing using combinatorial genetic markers together with a new large volume color imaging approach to study astrocyte development in the mouse cortex. We show that cortical astrocyte clones intermix with their neighbors and display extensive variability in terms of spatial organization, number and subtypes of cells generated. Clones develop through 3D spatial dispersion, while at the individual level astrocytes acquire progressively their complex morphology. Furthermore, we find that the astroglial network is supplied both before and after birth by ventricular progenitors that scatter in the neocortex and can give rise to protoplasmic as well as pial astrocyte subtypes. Altogether, these data suggest a model in which astrocyte precursors colonize the neocortex perinatally in a non-ordered manner, with local environment likely determining astrocyte clonal expansion and final morphotype.

Identification of region-specific astrocyte subtypes at single cell resolution

“…These subtypes could be formed from a common class of progenitor, defined by early patterning events and diversified by cues from neighboring CNS cells, such as neuronal release of sonic hedgehog (Shh) 49,50 . Alternatively, they may be formed from distinct classes of progenitor, which intermix in the cortex 51 . However, in this latter scenario it is interesting to note that the morphological development of clonally-related astrocytes also appears to be strongly influenced by local environment 51 .…”

“…Alternatively, they may be formed from distinct classes of progenitor, which intermix in the cortex 51 . However, in this latter scenario it is interesting to note that the morphological development of clonally-related astrocytes also appears to be strongly influenced by local environment 51 . A potential role for signals commonly associated with development (such as Shh signaling) is interesting, as evidence suggests that persistent activation of these pathways is necessary to maintain astrocyte diversity 52 .…”

Features Of Hippocampal Astrocytic Domains And Their Spatial Relation To Excitatory And Inhibitory Neurons

“…The investigation of astrocytic morphology to date was hindered mainly by technical barriers (Yu et al, 2020). In a recently published work, imaging of serially sectioned cortex using ChroMS microscopy followed the development of astrocytic clones and the 3D morphology of young and more mature astrocytes in these cortical clones (Clavreul et al, 2019). Brain clearing techniques now give access to large scale 3D imaging of fluorescently tagged cells, and specifically allow simultaneous imaging of more than one population.…”

No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience

“…Multiple astrocyte morphologies may be found in the same brain region [9]. Generally speaking, individual astrocytes are thought to occupy distinct, non-overlapping spatial locations in the tissue (so-called tiling), with only minimal overlap between the ends of astrocyte processes [11], although a recent report using clonal analysis suggests that up to 20% of astrocytes show considerable spatial overlap in cortex [12]. Astrocyte density can vary considerably between regions [10,13], although individual cell counts always depend on the histological methodologies applied, which needs to be considered when comparing studies.…”