Evidence map›Paper›PMID 32735824›Full record

ArticleStem cell reports2020

Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease.

Richard M Giadone, Derek C Liberti, Taylor M Matte, Jessica D Rosarda, Celia Torres-Arancivia, Sabrina Ghosh, Jolene K Diedrich, Sandra Pankow, Nicholas Skvir, J C Jean and 6 more

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

Article in Stem cell reports, 2020. 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
0.8field-weighted citation impact, top 29% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

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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

16 authors at 2 institutions in 1 country.

Richard M GiadoneCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA.
Derek C LibertiCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA.
Taylor M MatteCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA.
Jessica D RosardaDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Celia Torres-AranciviaAlan and Sandra Gerry Amyloid Research Laboratory, Amyloidosis Center, Boston University School of Medicine, Boston, MA, USA.
Sabrina GhoshCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA.
Jolene K DiedrichDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Sandra PankowDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Nicholas SkvirCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA.
J C JeanCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
John R YatesDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Andrew A WilsonCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Lawreen H ConnorsAlan and Sandra Gerry Amyloid Research Laboratory, Amyloidosis Center, Boston University School of Medicine, Boston, MA, USA.
Darrell N KottonCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
R Luke WisemanDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
George J MurphyCenter for Regenerative Medicine of Boston University and Boston Medical Center, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology and Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: gjmurphy@bu.edu.
Boston University · USScripps Research Institute · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
TrainingP41GM103533 · NIGMS · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 2012 to 2021
$20.7M
Direct Regulation of Extracellular Proteostasis by the Unfolded Protein ResponseR01NS092829 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI WISEMAN, ROCKLAND LUKE · 2015 to 2019
$2.1M
The CFTR InteractomeR01HL131697 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI YATES III, JOHN R · 2016 to 2019
$1.9M
TARGETING ENDOGENOUS SIGNALING PATHWAYS TO AMELIORATE SYSTEMIC AMYLOIDOSESR01DK102635 · NIDDK · SCRIPPS RESEARCH INSTITUTE, THE · PI MURPHY, GEORGE J, WISEMAN, ROCKLAND LUKE · 2014 to 2017
$823k
Novel Therapeutic Strategies in the Understanding of Systemic Amyloid DiseaseF31DK121481 · NIDDK · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GIADONE, RICHARD · 2019 to 2020
$67k
NCATS NIH HHS UL1 TR001430NHLBI NIH HHS R01 HL131697NIDDK NIH HHS F31 DK121481NIDDK NIH HHS R01 DK102635NIGMS NIH HHS P41 GM103533NINDS NIH HHS R01 NS092829
6 · The paper itself

Abstract

The systemic amyloidoses are diverse disorders in which misfolded proteins are secreted by effector organs and deposited as proteotoxic aggregates at downstream tissues. Although well described clinically, the contribution of synthesizing organs to amyloid disease pathogenesis is unknown. Here, we utilize hereditary transthyretin amyloidosis (ATTR amyloidosis) induced pluripotent stem cells (iPSCs) to define the contribution of hepatocyte-like cells (HLCs) to the proteotoxicity of secreted transthyretin (TTR). To this end, we generated isogenic, patient-specific iPSCs expressing either amyloidogenic or wild-type TTR. We combined this tool with single-cell RNA sequencing to identify hepatic proteostasis factors correlating with destabilized TTR production in iPSC-derived HLCs. By generating an ATF6 inducible patient-specific iPSC line, we demonstrated that enhancing hepatic ER proteostasis preferentially reduces the secretion of amyloidogenic TTR. These data highlight the liver's capacity to chaperone misfolded TTR prior to deposition, and moreover suggest the potential for unfolded protein response modulating therapeutics in the treatment of diverse systemic amyloidoses.

Indexed as

Models, BiologicalProteostasisActivating Transcription Factor 6AmyloidAmyloid Neuropathies, FamilialGene EditingGene Expression RegulationHepatocytesHumansInduced Pluripotent Stem CellsLiverMutationPrealbuminPromoter Regions, GeneticProtein StabilitySequence Analysis, RNAActivating Transcription Factor 6AmyloidATF6 protein, humanPrealbuminTransferrinamyloidgene editinghepatic diseasehereditary amyloidosispluripotent stem cellsprotein folding disordersproteostasissingle cell RNA sequencingtransthyretinunfolded protein response

Identifiers

PMID32735824
PMCPMC7419739
OpenAlexW3045797597

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.