Transcriptional profiling of astrocyte subtypes in naive mice and during experimental autoimmune encephalomyelitis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE136358 | GEO | 2021/01/18
REPOSITORIES: GEO
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Project description:Neurogenic astroglia-like cells of the prospective white matter (PWM) generate interneurons and astroglia during cerebellar development. However, the characterization of PWM subpopulations is still insufficient. Here we show that ACSA-2 (Astrocyte Cell Surface Antigen-2) is an intrinsic marker of astrocyte-committed precursors. In the developing cerebellum, the ontogeny of ACSA-2+ astrocytes revealed this epitope to be exclusively expressed by PWM cells. By contrast, in the adult brain, ACSA-2 is observed on parenchymal astrocytes, fibrous astrocytes of the white matter and at low level on Bergmann glia. In combination with GLAST, a marker for astroglia-like progenitors, we addressed the characteristics of neurogenic (ACSA-2-/GLAST+) and astrocyte-committed (ACSA-2+/GLAST+) precursors using transcriptomics and cell transplantation assays. Gene expression analyses identified major differences in genes related to the maturation status of astrocytes, their potential to generate interneurons and genes required for Bergmann glia specification. Transplantation assays further confirmed a divergent differentiation potential: ACSA-2+/GLAST+ cells, on the one side, differentiate into astrocytes and oligodendrocytes but not into Bergmann glia or neurons when transplanted into the neonatal cerebellum. On the other side, ACSA-2-/GLAST+ progenitors were able to generate interneurons and all the glial phenotypes. Moreover, ACSA-2-/GLAST+ progenitors even maintained the neurogenic potential when transplanted into the adult cerebellum. In conclusion, this work reports about ACSA-2, a marker for glial-restricted precursors of the PWM that in combination with GLAST enables for the discrimination and isolation of neurogenic and astrocyte-committed progenitors of the neonatal cerebellum.
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Project description:Astrocytes play many important functions in response to spinal cord injury (SCI) in an activated manner, including clearance of necrotic tissue, formation of protective barrier, maintenance of microenvironment balance, interaction with immune cells, and formation of the glial scar. More and more studies have shown that the astrocytes are heterogeneous, such as inflammatory astrocyte 1 (A1) and neuroprotective astrocyte 2 (A2) types. However, the subtypes of astrocyte resulting from SCI have not been clearly defined. In this study, using single-cell RNA sequencing, we constructed the transcriptomic profile of astrocytes from uninjured spinal cord tissue and nearby the lesion epicenter at 0.5, 1, 3, 7, 14, 60, and 90 days after mouse hemisection spinal cord tissue. Our analysis uncovered six transcriptionally distinct astrocyte states, including Atp1b2+, S100a4+, Gpr84+, C3+/G0s2+, GFAP+/Tm4sf1+, and Gss+/Cryab+ astrocytes. We used these new signatures combined with canonical astrocyte markers to determine the distribution of morphological and physiologically distinct for each astrocyte population at injured sites by immunofluorescence staining. Then we identified the dynamic evolution process of each astrocyte subtype following SCI. Finally, we also revealed the evolution of highly expressed genes in these astrocyte subtypes at different phases of SCI. Together, we provided six astrocyte subtypes at single-cell resolution following SCI. These data not only contribute to understanding the heterogeneity of astrocytes during SCI but also help to find new astrocyte subtypes as a target for SCI repair.
2021-11-21 | GSE189070 | GEO
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