Evidence map›Paper›PMID 31148215›Full record

ArticleAmerican journal of hematology2019

Generation of an immortalized erythroid progenitor cell line from peripheral blood: A model system for the functional analysis of Plasmodium spp. invasion.

Erik J Scully, Estela Shabani, Gabriel W Rangel, Christof Grüring, Usheer Kanjee, Martha A Clark, Mudit Chaand, Ryo Kurita, Yukio Nakamura, Marcelo U Ferreira and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in American journal of hematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 40 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

11 authors at 5 institutions in 4 countries.

Erik J ScullyDepartment of Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts.
Estela ShabaniDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Gabriel W RangelDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Christof GrüringDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Usheer KanjeeDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.ORCID 0000-0002-3169-4557
Martha A ClarkDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Mudit ChaandDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Ryo KuritaDepartment of Research and Development, Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan.
Yukio NakamuraCell Engineering Division, RIKEN BioResource Center, Ibaraki, Japan.
Marcelo U FerreiraDepartment of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Manoj T DuraisinghDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.ORCID 0000-0001-8534-5515
Harvard University · USBroad Institute · USJapanese Red Cross Society, Japan · JPRIKEN BioResource Research Center · JPUniversidade de São Paulo · BR

Funding

Functional analysis of red blood cell determinants of Plasmodium invasionR01HL139337 · NHLBI · HARVARD SCHOOL OF PUBLIC HEALTH · PI DURAISINGH, MANOJ T · 2017 to 2020
$2.3M
Elucidating ligand-receptor interactions required for Plasmodium vivax blood-stage infectionR01AI140751 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI DURAISINGH, MANOJ T · 2018 to 2022
$2.0M
Broad InstituteConselho Nacional de Desenvolvimento Científico e TecnológicoNational Science FoundationNHLBI NIH HHS R01 HL139337NIAID NIH HHS R01 AI140751Swiss National Science Foundation
6 · The paper itself

Abstract

Malaria pathogenesis is caused by the replication of Plasmodium parasites within the red blood cells (RBCs) of the vertebrate host. This selective pressure has favored the evolution of protective polymorphisms in erythrocyte proteins, a subset of which serve as cognate receptors for parasite invasion ligands. Recently, the generation of RBCs from immortalized hematopoietic stem cells (HSCs) has offered a more tractable system for genetic manipulation and long-term in vitro culture, enabling elucidation of the functional determinants of host susceptibility in vitro. Here we report the generation of an immortalized erythroid progenitor cell line (EJ cells) from as few as 100 000 peripheral blood mononuclear cells. It offers a robust method for the creation of customized model systems from small volumes of peripheral blood. The EJ cell differentiation mirrored erythropoiesis of primary HSCs, yielding orthochromatic erythroblasts and enucleated RBCs after eight days (ejRBCs). The ejRBCs supported invasion by both P. vivax and P. falciparum. To demonstrate the genetic tractability of this system, we used CRISPR/Cas9 to disrupt the Duffy Antigen/Receptor for Chemokines (DARC) gene, which encodes the canonical receptor of P. vivax in humans. Invasion of P. vivax into this DARC-knockout cell line was strongly inhibited providing direct genetic evidence that P. vivax requires DARC for RBC invasion. Further, genetic complementation of DARC restored P. vivax invasion. Taken together, the peripheral blood immortalization method presented here offers the capacity to generate biologically representative model systems for studies of blood-stage malaria invasion from the peripheral blood of donors harboring unique genetic backgrounds, or rare polymorphisms.

Indexed as

Erythroid Precursor CellsMalaria, FalciparumMalaria, VivaxModels, BiologicalPeripheral Blood Stem CellsCell Line, TransformedHumansPlasmodium falciparumPlasmodium vivax

Identifiers

PMID31148215
PMCPMC6984401
OpenAlexW2947271965

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.