Non-neuronal lineage-specific mRNAs

Non-neuronal lineage-specific mRNAs refer to the collective set of messenger RNA transcripts that define and maintain the identity of non-neuronal cells, such as astrocytes, fibroblasts, and microglia. In the context of regenerative medicine and cell reprogramming, these mRNAs represent a critical barrier to transdifferentiation; their active suppression is required to allow the expression of the neuronal gene program (Mall et al., 2017). Master regulators such as the transcription factor Myt1l, the microRNA miR-124, and the splicing factor PTBP1 function by directly or indirectly targeting these non-neuronal transcripts for degradation or translational repression (Conaco et al., 2006; Qian et al., 2020). Therapeutic strategies, including antisense oligonucleotides (ASOs) and gene therapies, aim to downregulate these lineage-specific programs to convert endogenous glial cells into functional neurons in situ. This approach holds significant potential for treating neurodegenerative disorders and brain injuries by replenishing lost neuronal populations. However, challenges include ensuring the complete shutdown of the original cell program and avoiding off-target effects in non-target tissues (Wang et al., 2021).

Other names

Non-neuronal transcriptsSomatic lineage programsNon-neuronal gene signaturesNon-neuronal lineage-specific genes

Suppression of non-neuronal identity through RNA interference, transcriptional repression, or splicing modulation to facilitate neuronal transdifferentiation.