Evidence map›Paper›PMID 37774678›Full record

ArticleCell2023

Human microglial state dynamics in Alzheimer's disease progression.

Na Sun, Matheus B Victor, Yongjin P Park, Xushen Xiong, Aine Ni Scannail, Noelle Leary, Shaniah Prosper, Soujanya Viswanathan, Xochitl Luna, Carles A Boix and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 310 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
310citing papers in PubMed, 1 pooled it
45.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

310 citing papers in PubMed, 1 synthesis or guideline pooled it, 359 citations in OpenAlex.

  1. Pooled it
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  13. Human iPSC models revealResearch square · 2026
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250 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Na SunMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Matheus B VictorPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Yongjin P ParkMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Pathology and Laboratory Medicine, Department of Statistics, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, BC Cancer, Vancouver, BC, Canada.
Xushen XiongMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Aine Ni ScannailPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Noelle LearyPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Shaniah ProsperPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Soujanya ViswanathanPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Xochitl LunaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Carles A BoixMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Benjamin T JamesMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yosuke TanigawaMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kyriaki GalaniMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hansruedi MathysPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Xueqiao JiangPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ayesha P NgPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Li-Huei TsaiBroad Institute of MIT and Harvard, Cambridge, MA, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: lhtsai@mit.edu.
Manolis KellisMIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: manoli@mit.edu.
Broad Institute · USMassachusetts Institute of Technology · USRush University Medical Center · USUniversity of Pittsburgh · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Single Cell Transcriptomic and Epigenomic Dissection of Opioid and Cocaine Responses in HIVU01DA053631 · NIDA · BROAD INSTITUTE, INC. · PI HEIMAN, MYRIAM, KELLIS, MANOLIS · 2021 to 2025
$12.6M
Mapping the vulnerable locus coeruleus pathways in aging and ADU01AG077227 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Kwanghun Chung, Li-Huei Tsai · 2022 to 2026
$9.6M
Identification of TDP-43 Modifiers Through Single-Cell Transcriptional and Epigenomic Dissection of ALS and FTLD-MNDR01NS127187 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BELZIL, VERONIQUE, DONNELLY, CHRISTOPHER JAMES · 2021 to 2025
$9.1M
Epigenomic, transcriptional and cellular dissection of Alzheimer's variantsR01AG058002 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HYMAN, BRADLEY T., JAENISCH, RUDOLF · 2017 to 2021
$7.9M
Elucidating the Molecular Mechanisms of Neuropsychiatric Symptoms in Alzheimer's DiseaseR01AG062335 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2018 to 2022
$6.5M
Single-cell epigenomic and trancriptional dissection of sex-specific differences in Alzheimer’s DiseaseR01AG074003 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2021 to 2025
$5.4M
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG008155NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG058002NIA NIH HHS R01 AG062335NIA NIH HHS R01 AG067151NIA NIH HHS R01 AG074003NIA NIH HHS R56 AG067151NIA NIH HHS RF1 AG054012NIA NIH HHS RF1 AG054321NIA NIH HHS RF1 AG057473NIA NIH HHS RF1 AG062377NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG077227NIDA NIH HHS U01 DA053631NIMH NIH HHS R01 MH109978NIMH NIH HHS U01 MH119509NINDS NIH HHS R01 NS127187NINDS NIH HHS RF1 NS129032NINDS NIH HHS U01 NS110453NINDS NIH HHS UG3 NS115064NINDS NIH HHS UH3 NS115064
6 · The paper itself

Abstract

Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer's disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.

Indexed as

Alzheimer DiseaseMicrogliaEpigenomeGene Expression RegulationHumansInflammationTranscription FactorsTranscriptomeTranscription FactorsAlzheimer'scell statesdisease-stage responseinflammationiPSCsmicrogliasingle-celltranscription factors

Identifiers

PMID37774678
PMCPMC10644954
OpenAlexW4387142551

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.