Sleep need driven oscillation of glutamate synaptic phenotype DOI Creative Commons
Kaspar E. Vogt, Ashwinikumar Kulkarni,

Richa Pandi

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 14, 2025

Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of synaptic sleep response. We report an increased AMPA/NMDA EPSC ratio frontal-cortical pyramidal neurons layers 2–3. Silent synapses are absent, decreasing plastic potential to convert silent NMDA active AMPA synapses. These changes recovered by sleep. genes enriched for shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, primarily observed excitatory projecting intra-telencephalically. controlled transcription factor, MEF2c, its repressor, HDAC4. can thus provide a framework within which motor learning training occur mediated sleep-dependent oscillation glutamate-synaptic phenotypes.

Language: Английский

Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender DOI
Stephen J. Fleming, Mark Chaffin, Alessandro Arduini

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(9), P. 1323 - 1335

Published: Aug. 7, 2023

Language: Английский

Citations

339
Selective vulnerability of layer 5a corticostriatal neurons in Huntington’s disease DOI Creative Commons
Christina Pressl, Kärt Mätlik,

Laura Kus

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(6), P. 924 - 941.e10

Published: Jan. 17, 2024

The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, nature somatic CAG expansions mHTT these cells, and their importance CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, single-nucleus RNA sequencing (snRNA-seq) motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors selected cingulate, visual, insular, prefrontal cortices to demonstrate loss layer 5a pyramidal neurons HD. Extensive occur Betz layers 6a 6b resilient Retrograde tracing experiments macaque brains identify as corticostriatal cells. We propose enhanced expansion altered synaptic function act together cause disconnection selective neuronal vulnerability cerebral cortex.

Language: Английский

Citations

45
Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics DOI
Gunsagar S. Gulati,

Jeremy Philip D’Silva,

Yunhe Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31

Published: Aug. 21, 2024

Language: Английский

Citations

42
Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica DOI
Michael A. Skinnider, Matthieu Gautier, Yue Yang Teo

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 150 - 163

Published: June 19, 2024

Language: Английский

Citations

29
Aging activates escape of the silent X chromosome in the female mouse hippocampus DOI Creative Commons
Margaret Gadek, Cayce K. Shaw, Samira Abdulai-Saiku

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(10)

Published: March 5, 2025

Women live longer than men and exhibit less cognitive aging. The X chromosome contributes to sex differences, as females harbor an inactive (Xi) active (Xa), in contrast males with only Xa. Thus, reactivation of silent Xi genes may contribute differences. We use allele-specific, single-nucleus RNA sequencing show that aging remodels transcription the Xa across hippocampal cell types. Aging preferentially changed gene expression on X's relative autosomes. Select underwent activation, new escape cells including dentate gyrus, critical learning memory. Expression escapee Plp1, a myelin component, was increased hippocampus female mice parahippocampus women. AAV-mediated Plp1 elevation gyrus male improved cognition. Understanding how confer advantage could lead novel targets counter brain disease both sexes.

Language: Английский

Citations

8
The effect of background noise and its removal on the analysis of single-cell expression data DOI Creative Commons
Philipp Janssen, Zane Kliesmete, Beate Vieth

et al.

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: June 19, 2023

In droplet-based single-cell and single-nucleus RNA-seq experiments, not all reads associated with one cell barcode originate from the encapsulated cell. Such background noise is attributed to spillage cell-free ambient RNA or swapping events.

Language: Английский

Citations

39
Molecular features driving cellular complexity of human brain evolution DOI
Emre Caglayan, Fatma Ayhan, Yuxiang Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 620(7972), P. 145 - 153

Published: July 19, 2023

Language: Английский

Citations

38
Challenges and opportunities to computationally deconvolve heterogeneous tissue with varying cell sizes using single-cell RNA-sequencing datasets DOI Creative Commons
Sean K. Maden, Sang Ho Kwon, Louise A. Huuki-Myers

et al.

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Dec. 14, 2023

Abstract Deconvolution of cell mixtures in “bulk” transcriptomic samples from homogenate human tissue is important for understanding disease pathologies. However, several experimental and computational challenges impede transcriptomics-based deconvolution approaches using single-cell/nucleus RNA-seq reference atlases. Cells the brain blood have substantially different sizes, total mRNA, transcriptional activities, existing may quantify mRNA instead type proportions. Further, standards are lacking use atlases integrative analyses single-cell spatial transcriptomics data. We discuss how to approach these key with orthogonal “gold standard” datasets evaluating methods.

Language: Английский

Citations

25
Lost in space: what single-cell RNA sequencing cannot tell you DOI Creative Commons
Kelvin Adema, Michael A. Schon, Michael D. Nodine

et al.

Trends in Plant Science, Journal Year: 2024, Volume and Issue: 29(9), P. 1018 - 1028

Published: April 2, 2024

Plant scientists are rapidly integrating single-cell RNA sequencing (scRNA-seq) into their workflows. Maximizing the potential of scRNA-seq requires a proper understanding spatiotemporal context cells. However, positional information is inherently lost during scRNA-seq, limiting its to characterize complex biological systems. In this review we highlight how current analysis pipelines cannot completely recover spatial information, which confounds interpretation. Various strategies exist identify location RNA, from classical in situ hybridization transcriptomics. Herein discuss possibility utilizing supervise analyses. An integrative approach will maximize each technology, and lead insights go beyond capability individual technology.

Language: Английский

Citations

11
The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics DOI Creative Commons
Lukas M. Weber, Heena R. Divecha, Matthew N. Tran

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 24, 2024

Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout central nervous system, playing critical roles arousal and mood, as well various components of cognition including attention, learning, memory. The LC-NE system is also implicated multiple neurological neuropsychiatric disorders. Importantly, are highly sensitive to degeneration both Alzheimer’s Parkinson’s disease. Despite clinical importance brain region prominent role a variety behavioral functions, detailed molecular characterization LC lacking. Here, we used combination spatially-resolved transcriptomics single-nucleus RNA-sequencing characterize landscape transcriptomic profile human brain. We provide freely accessible resource these data web-accessible downloadable formats.

Language: Английский

Citations

8