Evidence map›Paper›PMID 40494892›Full record

ArticleNature communications2025

Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC.

Songlei Liu, Li Li, Fan Zhang, Mariana Garcia-Corral, Katharina Meyer, Patrick R J Fortuna, Björn van Sambeek, Evan Appleton, Alex H M Ng, Parastoo Khoshakhlagh and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Songlei Liu *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8607-8260
Li Li *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0002-5937-9679
Fan Zhang *Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6102-2970
Mariana Garcia-Corral *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0691-7157
Katharina MeyerDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9051-1354
Patrick R J FortunaDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Björn van SambeekDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7230-8755
Evan AppletonDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9378-5913
Alex H M NgDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Parastoo KhoshakhlaghDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Yuancheng Ryan LuWhitehead Institute for Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5982-3963
James CameronWhitehead Institute for Biomedical Research, Cambridge, MA, USA.
Ricardo N RamirezDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Yuting ChenDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0436-8876
Chun-Ting WuDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jeremy Y HuangDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6847-3109
Yuqi TanDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7200-3222
George ChaoDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7753-0323
John AachDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Elaine T LimDepartment of Medicine, Division of Innate Immunity University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-3651-0654
Jenny M TamDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. jenny.tam@wyss.harvard.edu.ORCID http://orcid.org/0000-0002-3767-7205
Soumya RaychaudhuriCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA. soumya@broadinstitute.org.ORCID http://orcid.org/0000-0002-1901-8265
George M ChurchDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0001-6232-9969

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Discovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4M
Integrative modelling of single-cell data to elucidate the genetic architecture of complex diseaseR01HG013083 · NHGRI · DANA-FARBER CANCER INST · PI ALEXANDER GUSEV, ALKES L PRICE · 2024 to 2026
$1.5M
NHGRI NIH HHS R01 HG013083NHGRI NIH HHS RM1 HG008525NIAMS NIH HHS R01 AR063759
6 · The paper itself

Abstract

Differentiation of induced pluripotent stem cells (iPSCs) into specialized cell types is essential for uncovering cell-type specific molecular mechanisms and interrogating cellular function. Transcription factor screens have enabled efficient production of a few cell types; however, engineering cell types that require complex transcription factor combinations remains challenging. Here, we report an iterative, high-throughput single-cell transcription factor screening method that enables the identification of transcription factor combinations for specialized cell differentiation, which we validated by differentiating human microglia-like cells. We found that the expression of six transcription factors, SPI1, CEBPA, FLI1, MEF2C, CEBPB, and IRF8, is sufficient to differentiate human iPSC into cells with transcriptional and functional similarity to primary human microglia within 4 days. Through this screening method, we also describe a novel computational method allowing the exploration of single-cell RNA sequencing data derived from transcription factor perturbation assays to construct causal gene regulatory networks for future cell fate engineering.

Indexed as

Cell DifferentiationInduced Pluripotent Stem CellsMicrogliaTranscription FactorsCells, CulturedGene Regulatory NetworksHigh-Throughput Screening AssaysHumansInterferon Regulatory Factor-8Interferon Regulatory FactorsSingle-Cell AnalysisInterferon Regulatory Factor-8Interferon Regulatory FactorsTranscription Factors

Identifiers

PMID40494892
PMCPMC12152180

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.