Human Alzheimer’s disease reactive astrocytes exhibit a loss of homeostastic gene expression DOI Creative Commons
David Dai, Mingyao Li, Edward B. Lee

и другие.

Acta Neuropathologica Communications, Год журнала: 2023, Номер 11(1)

Опубликована: Авг. 2, 2023

Astrocytes are one of the brain's major cell types and responsible for maintaining neuronal homeostasis via regulating extracellular environment, providing metabolic support, modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer's disease, astrocytes can take on a hypertrophic appearance. These reactive canonically associated with increases in cytoskeletal proteins, glial fibrillary acidic protein vimentin. However, molecular alterations that characterize human disease tissues have not been extensively studied single resolution. Using nucleus RNA sequencing data from normal, pathologic aging, brains, we identified transcriptomic changes astrocytes. Deep learning-based clustering algorithms denoised expression 17,012 genes clustered 15,529 astrocyte nuclei, identifying protoplasmic, gray matter fibrous, white clusters. trajectory analyses revealed spectrum reactivity within protoplasmic characterized by modest increase marked decrease homeostatic genes. Amyloid but tau pathology correlated reactivity. To identify reactivity-associated genes, linear regressions gene versus were used to top 52 upregulated 144 downregulated Gene Ontology analysis cellular growth, responses metal ions, inflammation, proteostasis. Downregulated involved interactions, development, ERBB signaling, synapse regulation. Transcription factors significantly enriched among co-immunofluorescence staining brain tissues, confirmed downregulation ERBB4 transcription factor NFIA Our findings reveal exist is strong loss normal function.

Язык: Английский

Learning-associated astrocyte ensembles regulate memory recall DOI
Michael R. Williamson, Wookbong Kwon, Junsung Woo

и другие.

Nature, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Язык: Английский

Процитировано

16
A comprehensive spatio-cellular map of the human hypothalamus DOI Creative Commons
John A. Tadross, Lukas Steuernagel, Georgina K.C. Dowsett

и другие.

Nature, Год журнала: 2025, Номер 639(8055), С. 708 - 716

Опубликована: Фев. 5, 2025

Abstract The hypothalamus is a brain region that plays key role in coordinating fundamental biological functions 1 . However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies 2,3 Here we combine single-nucleus sequencing 433,369 human hypothalamic cells with spatial transcriptomics, generating comprehensive spatio-cellular transcriptional map hypothalamus, ‘HYPOMAP’. Although conservation neuronal cell types between humans mice, as based on transcriptomic identity, generally high, there are notable exceptions. Specifically, significant disparities identity pro-opiomelanocortin neurons expression levels G-protein-coupled receptors two species carry direct implications for currently approved obesity treatments. Out 452 types, find 291 clusters significantly enriched body mass index (BMI) genome-wide association study genes. This enrichment driven by 426 ‘effector’ Rare deleterious variants six these ( MC4R , PCSK1 POMC CALCR BSN CORO1A ) associate BMI at population level, has not been linked previously to BMI. Thus, HYPOMAP provides detailed atlas context serves an important resource identify new druggable targets treating wide range conditions, including reproductive, circadian metabolic disorders.

Язык: Английский

Процитировано

4
Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects DOI
Bushra Bashir, Monica Gulati, Sukriti Vishwas

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102689 - 102689

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

2
Astrocyte heterogeneity and interactions with local neural circuits DOI Creative Commons
Matthew G. Holt

Essays in Biochemistry, Год журнала: 2023, Номер 67(1), С. 93 - 106

Опубликована: Фев. 7, 2023

Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into neuropil, where they interact with a variety of other cell types, including neurons at synapses. now known to be active players in all aspects synaptic life cycle, synapse formation and elimination, maturation, maintenance homeostasis modulation transmission. Traditionally, astrocytes have been studied as homogeneous group cells. However, recent studies uncovered surprising degree heterogeneity their development function, suggesting that may matched support local circuits. Hence, better understanding astrocyte its implications needed understand brain function.

Язык: Английский

Процитировано

40
Human Alzheimer’s disease reactive astrocytes exhibit a loss of homeostastic gene expression DOI Creative Commons
David Dai, Mingyao Li, Edward B. Lee

и другие.

Acta Neuropathologica Communications, Год журнала: 2023, Номер 11(1)

Опубликована: Авг. 2, 2023

Astrocytes are one of the brain's major cell types and responsible for maintaining neuronal homeostasis via regulating extracellular environment, providing metabolic support, modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer's disease, astrocytes can take on a hypertrophic appearance. These reactive canonically associated with increases in cytoskeletal proteins, glial fibrillary acidic protein vimentin. However, molecular alterations that characterize human disease tissues have not been extensively studied single resolution. Using nucleus RNA sequencing data from normal, pathologic aging, brains, we identified transcriptomic changes astrocytes. Deep learning-based clustering algorithms denoised expression 17,012 genes clustered 15,529 astrocyte nuclei, identifying protoplasmic, gray matter fibrous, white clusters. trajectory analyses revealed spectrum reactivity within protoplasmic characterized by modest increase marked decrease homeostatic genes. Amyloid but tau pathology correlated reactivity. To identify reactivity-associated genes, linear regressions gene versus were used to top 52 upregulated 144 downregulated Gene Ontology analysis cellular growth, responses metal ions, inflammation, proteostasis. Downregulated involved interactions, development, ERBB signaling, synapse regulation. Transcription factors significantly enriched among co-immunofluorescence staining brain tissues, confirmed downregulation ERBB4 transcription factor NFIA Our findings reveal exist is strong loss normal function.

Язык: Английский

Процитировано

39