In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.
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http://dx.doi.org/10.1016/j.stemcr.2024.10.001 | DOI Listing |
Plant Cell Physiol
December 2024
RIKEN Center for Sustainable Resource Science, Yokohama 230-0045, Japan.
Soybean (Glycine max) is a leguminous crop cultivated worldwide that accumulates high levels of isoflavones. Although previous research has often focused on increasing the soybean isoflavone content because of the estrogen-like activity of dietary soy in humans, the rapidly increasing demand for soybean as a plant-based meat substitute has raised concerns about excessive isoflavone intake. Therefore, the production of isoflavone-free soybean has been anticipated.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.
View Article and Find Full Text PDFBackground: The earliest recognized biomarker of AD is deposition of Aβ amyloid that leads to formation of plaques and may, over time, trigger or at least be followed by gliosis/neuroinflammation and neurofibrillary tangles, accompanied by neurodegenerative changes including neuronal and synaptic loss. We have previously reported that semaphorin 4D (SEMA4D), the major ligand of plexin B receptors expressed on astrocytes, is upregulated in diseased neurons during progression of AD and Huntington's disease (HD). Binding of SEMA4D to PLXNB receptors triggers astrocyte reactivity, leading to loss of neuroprotective homeostatic functions, including downregulation of glutamate and glucose transporters (doi:10.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
cheonan chungmu hospital, cheonan si, Korea, Republic of (South).
Background: Vascular contributions to dementia & Alzheimer's disease are increasing recognized. Recent studies have suggested that blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction, including the early clinical stages of AD. Apolipoprotein E4(APOE4), the major AD susceptibility gene, leads to accelerated blood-brain barrier breakdown & degeneration of brain capillary pericyte that maintain blood-brain barrier integrity.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, San Francisco, San Francisco, CA, USA.
Background: Mitochondrial DNA copy number (mtDNAcn) quantifies the number of mitochondria genomes per nucleated cell, with reduced mtDNAcn being associated with increased Alzheimer's disease (AD) neuropathology. Blood-based mtDNAcn has technical confounders, such as DNA purification, and biological confounders, such as compensatory upregulation of mtDNA. Therefore, we optimized a protocol for mtDNAcn quantification using droplet digital PCR (ddPCR) by testing (i) whole peripheral blood mononuclear cells (PBMCs) vs platelet-depleted PBMCs, (ii) column-based DNA extraction vs cell lysate, and (iii) mitochondrial DNA replication (mtDNArep).
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