Developing EasySci, a High-Throughput and Low-Cost Single-Cell Genomic Technique, to Study Aging and Alzheimer's Disease in Human and Mouse Brain
type: CreativeWork
description: Previous single-cell methods are limited by their relatively low throughput and high costs. This prevents most laboratories from performing large-scale cell profiling, complicating the understanding of rare cell type contributions to aging and disease. Moreover, these methods often focus on the 3' end of genes. Without capturing the complete gene body coverage, these technologies have limited detection of specific isoforms. To address these limitations, we extensively optimized a combinatorial indexing-based framework to develop EasySci. We used EasySci to study cell population dynamics associated with aging and Alzheimer's disease in the mammalian brain. This dataset recovered approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles from 20 mouse brains. An optimized clustering framework identified more than 300 distinct cell subtypes. This extensive cataloging revealed the molecular characteristics and spatial distribution of these subtypes, providing new insights into the cellular landscape of the brain. For instance, we identified the spatial locations of astrocyte and neuron subtypes, mapping them to distinct anatomical regions. We observed cell population shifts of rare cell types during aging, i.e. an expansion in inflammatory subtypes of microglia and oligodendrocytes. Contrary, neuronal and oligodendrocyte progenitor cell populations declined. In exploring the cellular response to Alzheimer's disease associated genetic mutations, we investigated the cell population dynamics of both established early-onset and novel late-onset Alzheimer's disease models. This comparison highlighted the late-onset Alzheimer's disease model, APOE*4/Trem2*R47H, having cell population dynamics reminiscent of the 5xFAD early-onset model. This suggests the novel model's potential utility in Alzheimer's disease research. For instance, the expansion of septal nuclei neurons were observed in both models. This neuron subtype had increased axono…
abstract: Previous single-cell methods are limited by their relatively low throughput and high costs. This prevents most laboratories from performing large-scale cell profiling, complicating the understanding of rare cell type contributions to aging and disease. Moreover, these methods often focus on the 3' end of genes. Without capturing the complete gene body coverage, these technologies have limited detection of specific isoforms. To address these limitations, we extensively optimized a combinatorial indexing-based framework to develop EasySci. We used EasySci to study cell population dynamics associated with aging and Alzheimer's disease in the mammalian brain. This dataset recovered approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles from 20 mouse brains. An optimized clustering framework identified more than 300 distinct cell subtypes. This extensive cataloging revealed the molecular characteristics and spatial distribution of these subtypes, providing new insights into the cellular landscape of the brain. For instance, we identified the spatial locations of astrocyte and neuron subtypes, mapping them to distinct anatomical regions. We observed cell population shifts of rare cell types during aging, i.e. an expansion in inflammatory subtypes of microglia and oligodendrocytes. Contrary, neuronal and oligodendrocyte progenitor cell populations declined. In exploring the cellular response to Alzheimer's disease associated genetic mutations, we investigated the cell population dynamics of both established early-onset and novel late-onset Alzheimer's disease models. This comparison highlighted the late-onset Alzheimer's disease model, APOE*4/Trem2*R47H, having cell population dynamics reminiscent of the 5xFAD early-onset model. This suggests the novel model's potential utility in Alzheimer's disease research. For instance, the expansion of septal nuclei neurons were observed in both models. This neuron subtype had increased axono…
author: Sziraki, Andras
keywords: single-cell transcriptomics, chromatin accessibility, aging, Alzheimer's disease (AD), EasySci, pericyte markers, Life Sciences
date published: 2024-01-01T08:00:00Z
date modified: 2026-07-24T04:10:53Z
provider: Rockefeller
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rockefeller