Evidence map›Paper›PMID 30717806›Full record

ArticleClinical epigenetics2019

Tracking of epigenetic changes during hematopoietic differentiation of induced pluripotent stem cells.

Olivia Cypris, Joana Frobel, Shivam Rai, Julia Franzen, Stephanie Sontag, Roman Goetzke, Marcelo A Szymanski de Toledo, Martin Zenke, Wolfgang Wagner

Abstract readComparative Study
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 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

9 authors.

Olivia CyprisHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.
Joana FrobelHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.
Shivam RaiHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.
Julia FranzenHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.
Stephanie SontagInstitute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Roman GoetzkeHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany.
Marcelo A Szymanski de ToledoInstitute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Martin ZenkeInstitute for Biomedical Engineering - Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Wolfgang WagnerHelmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstraße 20, 52074, Aachen, Germany. wwagner@ukaachen.de.ORCID 0000-0002-1971-3217

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDifferentiation of induced pluripotent stem cells (iPSCs) toward hematopoietic progenitor cells (HPCs) raises high hopes for disease modeling, drug screening, and cellular therapy. Various differentiation protocols have been established to generate iPSC-derived HPCs (iHPCs) that resemble their primary counterparts in morphology and immunophenotype, whereas a systematic epigenetic comparison was yet elusive.

resultsIn this study, we compared genome-wide DNA methylation (DNAm) patterns of iHPCs with various different hematopoietic subsets. After 20 days of in vitro differentiation, cells revealed typical hematopoietic morphology, CD45 expression, and colony-forming unit (CFU) potential. DNAm changes were particularly observed in genes that are associated with hematopoietic differentiation. On the other hand, the epigenetic profiles of iHPCs remained overall distinct from natural HPCs. Furthermore, we analyzed if additional co-culture for 2 weeks with syngenic primary mesenchymal stromal cells (MSCs) or iPSC-derived MSCs (iMSCs) further supports epigenetic maturation toward the hematopoietic lineage. Proliferation of iHPCs and maintenance of CFU potential was enhanced upon co-culture. However, DNAm profiles support the notion that additional culture expansion with stromal support did not increase epigenetic maturation of iHPCs toward natural HPCs.

conclusionDifferentiation of iPSCs toward the hematopoietic lineage remains epigenetically incomplete. These results substantiate the need to elaborate advanced differentiation regimen while DNAm profiles provide a suitable measure to track this process.

Indexed as

DNA MethylationCell DifferentiationCell ProliferationCells, CulturedCoculture TechniquesEpigenesis, GeneticHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsLeukocyte Common AntigensMesenchymal Stem CellsLeukocyte Common AntigensPTPRC protein, humanDNA methylationEpigeneticHematopoiesisHematopoietic differentiationInduced pluripotent stem cellsMesenchymal stromal cellsStromal support

Identifiers

PMID30717806
PMCPMC6360658

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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.