ArticleGenome biology2021
Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Cryptic DNA sequences encode a temperature sensor to regulate mitochondrial suicide during neuronal differentiation.Cell communication and signaling : CCS · 2026Article
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- Mitochondria facilitate neuronal differentiation by metabolising nuclear-encoded RNA.Cell communication and signaling : CCS · 2024Article
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- Neural differentiation in perspective: mitochondria as early programmers.Frontiers in neuroscience · 2024Review
- Redox-Mediated Rewiring of Signalling Pathways: The Role of a Cellular Clock in Brain Health and Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Interdependent Transcription of a Natural Sense/Antisense Transcripts Pair (Non-coding RNA · 2022Article
- Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes.Genome biology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransdifferentiation describes transformation in vivo of specialized cells from one lineage into another. While there is extensive literature on forced induction of lineage reprogramming in vitro, endogenous mechanisms that govern transdifferentiation remain largely unknown. The observation that human microvascular pericytes transdifferentiate into neurons provided an opportunity to explore the endogenous molecular basis for lineage reprogramming.
resultsWe show that abrupt destabilization of the higher-order chromatin topology that chaperones lineage memory of pericytes is driven by transient global transcriptional arrest. This leads within minutes to localized decompression of the repressed competing higher-order chromatin topology and expression of pro-neural genes. Transition to neural lineage is completed by probabilistic induction of R-loops in key myogenic loci upon re-initiation of RNA polymerase activity, leading to depletion of the myogenic transcriptome and emergence of the neurogenic transcriptome.
conclusionsThese findings suggest that the global transcriptional landscape not only shapes the functional cellular identity of pericytes, but also stabilizes lineage memory by silencing the competing neural program within a repressed chromatin state.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.