Clonal Astrocytic Response to Cortical Injury

Abstract

Astrocytes are a heterogeneous population of glial cells with multifaceted roles in the central nervous system. Recently, the new method for the clonal analysis Star Track evidenced the link between astrocyte heterogeneity and lineage. Here, we tested the morphological response to mechanical injury of clonally related astrocytes using the Star Track approach, which labels each cell lineage with a specific code of colors. Histological and immunohistochemical analyses at 7 days post injury revealed a variety of morphological changes that were different among distinct clones. In many cases, cells of the same clone responded equally to the injury, suggesting the dependence on their genetic codification (intrinsic response). However, in other cases cells of the same clone responded differently to the injury, indicating their response to extrinsic factors. Thus, whereas some clones exhibited a strong morphological alteration or a high proliferative response to the injury, other clones located at similar distances to the lesion were apparently unresponsive. Concurrence of different clonal responses to the injury reveals the importance of the development determining the astrocyte features in response to brain injuries. These features should be considered to develop therapies that affect glial function.

Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome‐wide expression analysis

“…This brings us to the next level of analysis, namely aimed at subsets of astrocytes with specific properties. Indeed, astrocytes at juxtavascular positions, the population that is most proliferative after injury (Bardehle et al, ) is a subset with their own progenitors as recently demonstrated by clonal analysis (Martín‐López et al, ). This suggests that juxtavascular astrocytes may be a specific population of cerebral cortex astrocytes and isolation of this subset may then reveal to which extent these share even more similarities to the SEZ NSCs or rather are their own kind.…”

The diversity and disparity of the glial scar

“…These proliferative astrocytes were largely localized to juxtavascular sites, indicating that niche-specific cues may direct functional properties of reactive astrocytes (see Box 1). Interestingly, this proliferative population of reactive astrocytes was also shown by clonal analysis to be derived from distinct progenitors 20 , suggesting that one source of reactive astrocyte heterogeneity may be distinct cellular origins. In support of this, neural stem cell (NSC)-derived reactive astrocytes have been shown to contribute to glial scars in the brain 21 , while a recent study found little contribution of NSC-derived reactive astrocytes to SCI-induced glial scars 22 .…”

Cross‐talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury

“…Indeed, we observed CD45 + cells accumulating in the vessels in conditions with increased astrocyte proliferation, consistent with their failure to infiltrate. Interestingly, juxtavascular astrocytes share a common ancestor during development, as shown by clonal analysis [59], suggesting that they may differ from other astrocytes not only in their position, but also their intrinsic makeup. But which could be the factors of juxtavascular astrocytes regulating monocyte invasion?…”