Evidence map›Paper›PMID 33257861›Full record

ArticleNature biotechnology2021

A comprehensive library of human transcription factors for cell fate engineering.

Alex H M Ng, Parastoo Khoshakhlagh, Jesus Eduardo Rojo Arias, Giovanni Pasquini, Kai Wang, Anka Swiersy, Seth L Shipman, Evan Appleton, Kiavash Kiaee, Richie E Kohman and 12 more

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
9.3field-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

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.

  1. Pooled it
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  9. A highly penetrantbioRxiv : the preprint server for biology · 2026
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89 more citing papers are in PubMed but not listed here.

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

22 authors at 8 institutions in 5 countries.

Alex H M Ng *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Parastoo Khoshakhlagh *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jesus Eduardo Rojo AriasTechnische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.ORCID http://orcid.org/0000-0001-6098-3799
Giovanni PasquiniTechnische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.
Kai WangDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6240-0147
Anka SwiersyTechnische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.
Seth L ShipmanGladstone Institutes and University of California, San Francisco, San Francisco, CA, USA.
Evan AppletonDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9378-5913
Kiavash KiaeeDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Richie E KohmanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Andyna VernetWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Matthew DysartDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Kathleen LeeperDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1728-9683
Wren SaylorDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6806-7469
Jeremy Y HuangDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6847-3109
Amanda GravelineWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
Jussi TaipaleDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
David E HillDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5192-0921
Marc VidalDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Juan M Melero-MartinDepartment of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
Volker BusskampTechnische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany. volker.busskamp@ukbonn.de.ORCID http://orcid.org/0000-0001-7517-8944
George M ChurchDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0003-3535-2076
Harvard University · USBoston Children's Hospital · USTechnische Universität Dresden · DEDana-Farber/Harvard Cancer Center · USGladstone Institutes · USUniversity of Bonn · DEUniversity of Helsinki · FIWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6M
Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Vascular networks genetically engineered for protein drug deliveryR01HL128452 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI MELERO-MARTIN, JUAN M, WANG, BO · 2015 to 2024
$4.8M
Vascular niche bioengineering for human bone regenerationR01AR069038 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI MELERO-MARTIN, JUAN M · 2016 to 2020
$1.9M
Cancer Research UK 28801European Research Council 678071Medical Research Council MR/V000500/1NCI NIH HHS P30 CA006516NHGRI NIH HHS P50 HG005550NHGRI NIH HHS RM1 HG008525NHLBI NIH HHS R01 HL128452NIAMS NIH HHS R01 AR069038
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) offer an unprecedented opportunity to model diverse cell types and tissues. To enable systematic exploration of the programming landscape mediated by transcription factors (TFs), we present the Human TFome, a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms. By screening the library in three hPSC lines, we discovered 290 TFs, including 241 that were previously unreported, that induce differentiation in 4 days without alteration of external soluble or biomechanical cues. We used four of the hits to program hPSCs into neurons, fibroblasts, oligodendrocytes and vascular endothelial-like cells that have molecular and functional similarity to primary cells. Our cell-autonomous approach enabled parallel programming of hPSCs into multiple cell types simultaneously. We also demonstrated orthogonal programming by including oligodendrocyte-inducible hPSCs with unmodified hPSCs to generate cerebral organoids, which expedited in situ myelination. Large-scale combinatorial screening of the Human TFome will complement other strategies for cell engineering based on developmental biology and computational systems biology.

Indexed as

Alternative SplicingCell DifferentiationCell EngineeringCells, CulturedCellular Reprogramming TechniquesCoculture TechniquesHumansOligodendrogliaPluripotent Stem CellsSystems BiologyTranscription FactorsTranscription Factors

Identifiers

PMID33257861
PMCPMC7610615
OpenAlexW3107940478

What OpenQuestion holds

Textmetadata
LicenceTDM
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.