The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina

Pruvost, Mathilde; Patzig, Julia; Yattah, Camila; Selcen, Ipek; Hernandez, Marylens; Park, Hye-Jin; Moyon, Sarah; Liu, Shibo; Morioka, Malia S.; Shopland, Lindsay; Al-Dalahmah, Osama; Bendl, Jaroslav; Fullard, John F.; Roussos, Panos; Goldman, James; He, Ye; Dupree, Jeffrey L.; Casaccia, Patrizia

doi:10.1016/j.celrep.2023.112848

Cited by 9 publications

(7 citation statements)

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“…Tubb3 , a gene typically associated with neurons, has also been discovered in intermediate cells that lie between oligodendrocyte precursor cells (OPCs) and astrocytes (28). Furthermore, several other genes, including laminin subunit alpha ( Lmna ), CNPase ( Cnp ), and SRY-box transcription factor 10 ( Sox10 ), which are enriched in OPC ( Akay et al, 2021 ; Pruvost et al, 2023 ), were found in SC1 ( Figure 4B ). Specifically, as LMNA expression levels rise as OPCs differentiate ( Pruvost et al, 2023 ), SC1 may consist of some progenitor cells that differentiate into myelinating Schwann cells.…”

Section: Resultsmentioning

confidence: 99%

Differential transcriptional profiles of vagal sensory neurons in female and male mice

2024

Front. Neurosci.

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IntroductionDifferences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the vagus nerve ganglia innervate a variety of visceral organs and use specialized nerve endings to sense interoceptive signals. This visceral organ-brain axis plays a role in relaying interoceptive signals to higher brain centers, as well as in regulating the vago-vagal reflex. I hypothesized that molecularly distinct populations of vagal sensory neurons would play a role in causing differences in metabolic homeostasis between the sexes.MethodsSnRNA-Seq was conducted on dissociated cells from the vagus nerve ganglia using the 10X Genomics Chromium platform.ResultsSingle-nucleus RNA sequencing analysis of vagal sensory neurons from female and male mice revealed differences in the transcriptional profiles of cells in the vagus nerve ganglia. These differences are linked to the expression of sex-specific genes such as Xist, Tsix, and Ddx3y. Among the 13 neuronal clusters, one-fourth of the neurons in male mice were located in the Ddx3y-enriched VN1 and VN8 clusters, which displayed higher enrichment of Trpv1, Piezo2, Htr3a, and Vip genes. In contrast, 70% of the neurons in females were found in Xist-enriched clusters VN4, 6, 7, 10, 11, and 13, which showed enriched genes such as Fgfr1, Lpar1, Cpe, Esr1, Nrg1, Egfr, and Oprm1. Two clusters of satellite cells were identified, one of which contained oligodendrocyte precursor cells in male mice. A small population of cells expressed Ucp1 and Plin1, indicating that they are epineural adipocytes.DiscussionUnderstanding the physiological implications of distinct transcriptomic profiles in vagal sensory neurons on energy balance and metabolic homeostasis would help develop sex-specific treatments for obesity and metabolic dysregulation.

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Section: Resultsmentioning

confidence: 99%

Differential transcriptional profiles of vagal sensory neurons in female and male mice

2024

Front. Neurosci.

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“…The mRNA expression levels of Gdf15, Vim, and Lmna, important factors for myelinating function and axonal regeneration [19][20][21] , were increased in mice administered ASO-Zfp384 (Fig. 4f).…”

Section: Aso Against Zfp384 Promoted Neural Repair After Ischemic Strokementioning

confidence: 95%

Sustaining microglial reparative function enhances stroke recovery

Tsuyama,

Sakai,

Kurabayashi

et al. 2024

Preprint

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Neurological symptoms after brain injury can remain as lifelong detrimental sequelae since most spontaneous brain recovery disappears within a few months after brain injury. Microglia play an essential role in recovery processes after brain injury; however, cellular and molecular mechanisms that diminish spontaneous brain functional recovery remain unknown. We discovered by cellular fate analysis that reparative myeloid cells remained in the post-stroke brain even after losing their reparative function. ZFP384 was identified as a pivotal transcriptional regulator that diminished recovery phase-associated gene expression in reparative myeloid cells, turning them into ruined cells which lost reparative functions. ZFP384 diminished the YY1-mediated chromatin interaction necessary for expressing recovery phase-associated genes. Antisense oligonucleotide against Zfp384 sustained the broad range of neural repair effects of myeloid cells and enhanced stroke recovery, even in the chronic phase of ischemic stroke recovery. Thus, therapeutics preventing the myeloid reparative immunity from reaching a ruined state sustains brain functional recovery.

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“…Metabolite extraction from Drosophila larval brains was executed following a modified cold methanol method as previously described (Pruvost et al, 2023). For each biological replicate, a pool of 100 brains from third instar larvae of either wild type (Canton-S) or Obp44a -/- was dissected and combined in PBS buffer.…”

Section: Methodsmentioning

confidence: 99%

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developingDrosophilabrain

Yin,

Chen,

Grigsby-Brown

et al. 2024

Preprint

Self Cite

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Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins fromDrosophilaCNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

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The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina

Cited by 9 publications

References 122 publications

Differential transcriptional profiles of vagal sensory neurons in female and male mice

Differential transcriptional profiles of vagal sensory neurons in female and male mice

Sustaining microglial reparative function enhances stroke recovery

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developingDrosophilabrain

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