Cited by Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species DOI

John K. Mich, Smrithi Sunil, Nelson Johansen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 21, 2023

Abstract Proper brain function requires the assembly and of diverse populations neurons glia. Single cell gene expression studies have mostly focused on characterization neuronal diversity; however, recent revealed substantial diversity glial cells, particularly astrocytes. To better understand types their roles in neurobiology, we built a new suite adeno-associated viral (AAV)-based genetic tools to enable access astrocytes oligodendrocytes. These oligodendrocyte astrocyte enhancer-AAVs are highly specific (usually > 95% type specificity) with variable levels, our show multiple distinct patterns reflecting spatial distribution types. provide best glial-specific functional tools, several were: optimized for higher shown be rat macaque, maintain activity epilepsy where traditional promoters changed activity, used drive transgenes including Cre recombinase acetylcholine-responsive sensor iAChSnFR. The astrocyte-specific iAChSnFR clear reward-dependent acetylcholine response nucleus accumbens during reinforcement learning. Together, this collection will across species, disease states, behavioral epochs.

Language: Английский

Citations

Switch of innate to adaptative immune responses in the brain of patients with Alzheimer’s disease correlates with tauopathy progression DOI

Marcos R. Costa

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 18, 2024

Abstract Neuroinflammation is a key feature of Alzheimer’s disease (AD). In this work, analysis single- cell RNA-sequencing (scRNA-seq) data obtained from the brain patients with AD provides evidence supporting switch an innate to adaptative immune response during tauopathy progression, both disease-associated microglia (DAM) and CD8+ T cells becoming more frequent at advanced Braak stages.

Language: Английский

Citations

Cellular Underpinnings of the Selective Vulnerability of Tauopathic Insults in Alzheimer's Disease DOI

Justin Torok, Pedro D. Maia, Chaitali Anand

et al.

Published: Jan. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Language: Английский

Citations

Massive Attack: Can Biotechnology Turn a Bonanza of Data into a Boon? DOI

Mike May

GEN Biotechnology, Journal Year: 2024, Volume and Issue: 3(3), P. 107 - 110

Published: June 1, 2024

Language: Английский

Citations

Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS DOI

Yeganeh M. Marghi, Rohan Gala, Fahimeh Baftizadeh

et al.

Nature Computational Science, Journal Year: 2024, Volume and Issue: 4(9), P. 706 - 722

Published: Sept. 23, 2024

Language: Английский

Citations

Comparative gene regulatory network analysis in Alzheimer’s disease and major depressive disorder DOI

Hanne Puype, Joke Deschildre, Vanessa Vermeirssen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 23, 2023

Abstract Alzheimer’s disease and major depressive disorder are prevalent, devastating conditions with limited treatment options. Recent insights suggest that despite distinct phenotypes, these disorders share similar processes such as neuroinflammation. However, the extent of overlapping biological their underlying molecular mechanisms remain to be elucidated. Therefore, we adopted a computational systems biology approach compare regulatory programs in prefrontal cortex both disorders. Leveraging publicly available RNA sequencing data on different human cohorts, at bulk single-cell level, using diverse methodologies, inferred gene networks, which model interactions between transcription factors target genes, characterized cell-type-specific pathways. We identified core circuits shared disorders, including play pivotal role microglial activation IKZF1, IRF8, RUNX1 SPI1. Most had reported Alzheimer’s, but not depression. found several common pathways activation, also more disease-specific Through orthogonal analysis, were able validate predicted disorder. In summary, our work revealed neuroinflammation diseases, under control circuits. The potential relevance genes warrants additional investigation, especially depression, offering possible novel therapeutic opportunities.

Language: Английский

Citations

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance DOI

Geetika Aggarwal,

Theodore K. Malmstrom,

John E. Morley

et al.

npj Aging, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 9, 2023

Abstract We recently reported accelerated cognitive decline in Europeans aged > 70 years with low circulating adropin levels. Adropin is a small, secreted peptide that highly expressed the human nervous system. Expression profiling indicate relationships between expression brain and pathways affect dementia risk. Moreover, increased or treatment using synthetic improves cognition mouse models of aging. Here we report concentrations associate poor (worst quintile for composite score derived from MMSE semantic fluency test) late-middle community-dwelling African Americans (OR = 0.775, P < 0.05; age range 45–65 y, n 352). The binomial logistic regression controlled sex, age, education, cardiometabolic disease risk indicators, obesity. Previous studies cultured cells brains donors suggest high astrocytes. In snRNA-seq data middle temporal gyrus (MTG) donors, higher astrocytes relative to other cell types. all cell-types declines advance but not affected by status. astrocytes, also donor age. Additional analysis indicated positive correlations transcriptomic signatures energy metabolism protein synthesis are adversely suppressed pro-inflammatory factors. Collectively, these levels potential early indicator impairment. Declining plausible link aging, neuroinflammation, decline.

Language: Английский

Citations

Human disease-specific cell signatures in non-lesional tissue in Multiple Sclerosis detected by single-cell and spatial transcriptomics DOI

Matti Lam, Dylan I. Lee,

Ivy M Kosater

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

Recent investigations of cell type changes in Multiple Sclerosis (MS) using single-cell profiling methods have focused on active lesional and peri-lesional brain tissue, implicated a number peripheral central nervous system types. However, an important question is the extent to which so-called "normal-appearing" non-lesional tissue individuals with MS accumulate over lifespan. Here, we compared post-mortem from donors pathological or clinical diagnosis Religious Orders Study Rush Memory Aging Project (ROSMAP) cohorts age- sex-matched brains persons without (controls). We profiled three regions single-nucleus RNA-seq: dorsolateral prefrontal cortex (DLPFC), normal appearing white matter (NAWM) pulvinar thalamus (PULV), 15 control individuals, 8 MS, 5 other detrimental pathologies accompanied by demyelination, resulting total 78 samples. identified region- type-specific differences samples diagnosed and/or exhibiting secondary demyelination neurological conditions, as donors. These included lower proportions oligodendrocytes expression myelination related genes MOBP, MBP, PLP1, well higher CRYAB+ all regions. Among microglial signatures, subgroups that were both (TMEM163+/ERC2+), those specifically (HIF1A+/SPP1+) (SOCS6+/MYO1E+), grey matter. To validate our findings, generated Visium spatial transcriptomics data matched 13 donors, recapitulated observations gene microglia. Finally, show some observed between NAWM mirror previously reported WM lesions Overall, investigation sheds additional light type- disease-specific present even highlighting widespread cellular signatures may be associated downstream changes.

Language: Английский

Citations

Fast evolutionary turnover and overlapping variances of sex-biased gene expression patterns defy a simple binary classification of sexes DOI

Chen Xie, Sven Künzel, Diethard Tautz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 26, 2024

Abstract The phenotypic differences between the sexes are generated by genes with sex-biased expression. These range from a few major regulators to large numbers of organ-specific effector in sexually mature individuals. We explore variation and evolutionary patterns these dataset natural populations sub-species species mice across an distance two million years. Within short phylogenetic distances, we find faster turnover gene expression compared non-sex-biased adaptive protein evolution for that given taxon. show occur only subset co-expression modules each organ taxa occurs often within main modules. Given our is first animals was combined population genetic context, were interested study within-group variances somatic gonadal tissues their turnover. To visualize individual variances, have developed index (SBI) represents cumulative all organ. SBI distributions can close binary overlapping sexes. They do not correlate organs same individuals, thus supporting mosaic model sex-determination Comparison data humans shows fewer strongly conclude subject fast evolution, no long-term stability male or female characteristics.

Language: Английский

Citations

Genetic Algorithm Selection of Interacting Features (GASIF) for Selecting Biological Gene-Gene Interactions DOI

Rachit Kumar, David Zhang, Marylyn D. Ritchie

et al.

Proceedings of the Genetic and Evolutionary Computation Conference, Journal Year: 2024, Volume and Issue: unknown, P. 1282 - 1290

Published: July 8, 2024

Language: Английский

Citations