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Omics · study · 2026

Hopx is a dual-gatekeeper of astrocyte fate enabling in vivo reprogramming and neural repair

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Astrocyte-to-neuron conversion provides a potential strategy for neural repair, but the endogenous mechanisms that maintain astrocytic identity and restrict neuronal fate acquisition remain incompletely understood.

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In this study, we investigated the role of Hopx, an astrocyte-enriched transcriptional regulator, in maintaining astrocyte fate and limiting astrocyte-to-neuron conversion. We developed an AAV-compatible TIGR interference (TIGRi) system to repress Hopx expression in vivo and applied this strategy in Aldh1l1CreERT2;Rosa26-LSL-tdTomato lineage-tracing mice.

To define the transcriptional changes associated with Hopx knockdown-induced astrocyte-to-neuron conversion, we performed single-cell RNA sequencing on hippocampal cells collected after AAV-TIGRi-Hopx delivery and tamoxifen induction. scRNA-seq dataset was generated to characterize the transcriptomic states of virus-transduced astrocyte-lineage cells, identify intermediate cell populations during conversion, and reconstruct the trajectory from astrocyte-like cells toward progenitor-like and neuron-like states.

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The analysis revealed Hopx knockdown-associated induction of neurogenic and neuronal transcriptional programs in AAV-transduced astrocyte-lineage cells, including increased expression of progenitor- and neuron-associated markers and gene modules related to generation of neurons and neuron fate commitment. These data support the conclusion that Hopx repression promotes a progressive transcriptional transition from a glial state toward a neuron-like state and provide a transcriptomic resource for studying endogenous regulation of astrocyte plasticity during in vivo neural reprogramming.

In parallel, we performed HOPX ChIP-seq to define the genome-wide binding landscape of HOPX and identify HOPX peak-associated candidate genes. Together, the scRNA-seq and ChIP-seq datasets provide complementary resources for investigating the transcriptional and genomic regulatory mechanisms underlying astrocyte-to-neuron conversion in vivo.

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Life Sciences
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RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33318915 d agoJSON v1
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concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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