Evidence map›Paper›PMID 34836963›Full record

ArticleNature communications2021

CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease.

Emmanouela Tsagkaraki, Sarah M Nicoloro, Tiffany DeSouza, Javier Solivan-Rivera, Anand Desai, Lawrence M Lifshitz, Yuefei Shen, Mark Kelly, Adilson Guilherme, Felipe Henriques and 13 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 pooled it
6.7field-weighted citation impact, top 2% 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

56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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  17. The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
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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 at 2 institutions in 2 countries.

Emmanouela Tsagkaraki *Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0001-7754-8945
Sarah M Nicoloro *Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-8638-4556
Tiffany DeSouzaProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Javier Solivan-RiveraProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Anand DesaiProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Lawrence M LifshitzProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Yuefei ShenProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Mark KellyProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0001-9018-594X
Adilson GuilhermeProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0003-0535-5911
Felipe HenriquesProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-9245-7141
Nadia AmraniUniversity of Crete School of Medicine, Crete, 71003, Greece.
Raed IbraheimRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-0961-7299
Tomas C RodriguezRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-8724-5427
Kevin LukDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Stacy MaitlandDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Randall H FriedlineProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0003-0894-448X
Lauren TauerProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-2315-1050
Xiaodi HuProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Jason K KimProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-7185-042X
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-7042-201X
Erik J SontheimerProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.ORCID http://orcid.org/0000-0002-0881-0310
Silvia CorveraProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA. Silvia.Corvera@umassmed.edu.ORCID http://orcid.org/0000-0002-0009-4129
Michael P CzechProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA. Michael.Czech@umassmed.edu.ORCID http://orcid.org/0000-0003-4075-7350
University of Massachusetts Chan Medical School · USUniversity of Crete · GR

Funding

Insulin Signaling and Metabolic Regulation in AdipocytesR37DK030898 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CZECH, MICHAEL P · 1996 to 2021
$7.2M
Adipose Tissue Angiogenesis and Metabolic DiseaseR01DK089101 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CORVERA, SILVIA · 2011 to 2024
$5.7M
Next-generation antisense therapeutics for ALS and frontotemporal dementiaR01NS111990 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Robert H Brown, Jonathan K Watts · 2019 to 2026
$5.2M
UMass Mouse Metabolic Phenotyping Center - Metabolism CoreU2CDK093000 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2016 to 2021
$4.6M
Mechanisms of human adipose tissue development and impact of diabetesR01DK123028 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Silvia Corvera · 2019 to 2026
$3.6M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUH3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2021 to 2022
$3.1M
Insulin Signaling and Metabolic Regulation in AdipocytesR01DK030898 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CZECH, MICHAEL P · 1986 to 2011
$2.7M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUG3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2018 to 2020
$2.5M
Engineered Cas9 Nucleases with Single-Genomic-Site Precision for CYBB CorrectionR01GM115911 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SONTHEIMER, ERIK J., WOLFE, SCOT A · 2016 to 2019
$1.6M
Amelioration of Beta-hemoglobinopathies by efficient precise deletion of the +58 BCL11A enhancer using orthogonal Cas9-Cas9 chimerasF31HL147482 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUK, KEVIN · 2019 to 2020
$65k
NCATS NIH HHS UG3 TR002668NCATS NIH HHS UH3 TR002668NHLBI NIH HHS F31 HL147482NIDDK NIH HHS R01 DK030898NIDDK NIH HHS R01 DK089101NIDDK NIH HHS R01 DK123028NIDDK NIH HHS R37 DK030898NIDDK NIH HHS U2C DK093000NIGMS NIH HHS R01 GM115911NINDS NIH HHS R01 NS111990
6 · The paper itself

Abstract

Obesity and type 2 diabetes are associated with disturbances in insulin-regulated glucose and lipid fluxes and severe comorbidities including cardiovascular disease and steatohepatitis. Whole body metabolism is regulated by lipid-storing white adipocytes as well as "brown" and "brite/beige" adipocytes that express thermogenic uncoupling protein 1 (UCP1) and secrete factors favorable to metabolic health. Implantation of brown fat into obese mice improves glucose tolerance, but translation to humans has been stymied by low abundance of primary human beige adipocytes. Here we apply methods to greatly expand human adipocyte progenitors from small samples of human subcutaneous adipose tissue and then disrupt the thermogenic suppressor gene NRIP1 by CRISPR. Ribonucleoprotein consisting of Cas9 and sgRNA delivered ex vivo are fully degraded by the human cells following high efficiency NRIP1 depletion without detectable off-target editing. Implantation of such CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreases adiposity and liver triglycerides while enhancing glucose tolerance compared to implantation with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic enhancement of human adipocytes without exposing the recipient to immunogenic Cas9 or delivery vectors.

Indexed as

Adipocytes, BrownAdipocytes, WhiteAdult Stem CellsAnimalsCell Culture TechniquesCell DifferentiationCRISPR-Cas SystemsDiet, High-FatDisease Models, AnimalFatty LiverGene EditingGlucose IntoleranceHumansLipid MetabolismMaleMiceNRIP1 protein, humanNuclear Receptor Interacting Protein 1RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34836963
PMCPMC8626495
OpenAlexW3216964707

What OpenQuestion holds

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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.