Evidence map›Paper›PMID 37500887›Full record

ArticleNature immunology2023

Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro.

Michael-John Dolan, Martine Therrien, Saša Jereb, Tushar Kamath, Vahid Gazestani, Trevor Atkeson, Samuel E Marsh, Aleksandrina Goeva, Neal M Lojek, Sarah Murphy and 14 more

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

Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
17.4field-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

117 citing papers in PubMed, 142 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Human iPSC models revealResearch square · 2026
    Article
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  8. Review
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57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 3 countries.

Michael-John Dolan *Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Martine Therrien *Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3150-4052
Saša JerebStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Tushar KamathStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vahid GazestaniStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Trevor AtkesonStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samuel E MarshBoston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3012-6945
Aleksandrina GoevaStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Neal M LojekStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sarah MurphyBoston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA.
Cassandra M WhiteBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6697-4321
Julia JoungBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.
Bingxu LiuBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3661-3410
Francesco LimoneStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kevin EgganStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nir HacohenBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2349-2656
Bradley E BernsteinBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4344-3592
Ville LeinonenDepartment of Neurosurgery, Kuopio University Hospital and Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland.
Mathew Blurton-JonesDepartment of Neurobiology and Behavior, Sue and Bill Gross Stem Cell Research Center, UCI Institute for Memory Impairments and Neurological Disorders, Institute for Immunology, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-7770-7157
Feng ZhangBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0178-7995
Charles B EpsteinBroad Institute of MIT and Harvard Cambridge, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8358-8345
Evan Z MacoskoStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. emacosko@broadinstitute.org.ORCID http://orcid.org/0000-0002-2794-5165
Beth StevensStanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Beth.Stevens@childrens.harvard.edu.ORCID http://orcid.org/0000-0003-4226-1201
Broad Institute · USBoston Children's Hospital · USUniversity of California, Irvine · USUniversity of California San Diego · USUniversity of Eastern Finland · FI

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joshua Grill · 2020 to 2026
$27.9M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Characterizing the landscape of cell-type specific changes associated with Alzheimer's disease before death with single-cell genomicsF30AG069446 · NIA · HARVARD MEDICAL SCHOOL · PI KAMATH, TUSHAR VINOD · 2020 to 2023
$173k
Alzheimer's Association ADSF-21-831114-CHoward Hughes Medical InstituteNIA NIH HHS F30 AG069446NIA NIH HHS P30 AG066519NICHD NIH HHS P50 HD105351NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsNeurodegenerative DiseasesBrainHumansMicroglia

Identifiers

PMID37500887
PMCPMC10382323
OpenAlexW4385331538

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.