Evidence map›Paper›PMID 39197437›Full record

ArticleCells, tissues, organs2024

Robust Differentiation of Human Pluripotent Stem Cells into Lymphatic Endothelial Cells Using Transcription Factors.

Sanjoy Saha, Francine Graham, James Knopp, Christopher Patzke, Donny Hanjaya-Putra

Abstract read
In one paragraph

Article in Cells, tissues, organs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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  8. [Research on tissue regeneration and engineered scaffold materials in prevention and treatment of lymphedema].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
    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

5 authors.

Sanjoy SahaDepartment of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, Indiana, USA.
Francine GrahamDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana, USA.
James KnoppCenter for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, Indiana, USA.
Christopher PatzkeCenter for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, Indiana, USA.
Donny Hanjaya-PutraDepartment of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, Indiana, USA.

Funding

Engineering the Stem Cell Microenvironment for Lymphatic RegenerationR35GM143055 · NIGMS · UNIVERSITY OF NOTRE DAME · PI HANJAYA-PUTRA, DONNY · 2021 to 2025
$2.2M
NIGMS NIH HHS R35 GM143055
6 · The paper itself

Abstract

introductionGenerating new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, protocols to differentiate human induced pluripotent stem cells (hiPSCs) into lymphatic endothelial cells (LECs) are still lacking.

methodsTranscription factors, ETS2 and ETV2 are key regulators of embryonic vascular development, including lymphatic specification. While ETV2 has been shown to efficiently generate blood endothelial cells, little is known about ETS2 and its role in lymphatic differentiation. Here, we describe a method for rapid and efficient generation of LECs using transcription factors, ETS2 and ETV2.

resultsThis approach reproducibly differentiates four diverse hiPSCs into LECs with exceedingly high efficiency. Timely activation of ETS2 was critical, to enable its interaction with Prox1, a master lymphatic regulator. Differentiated LECs express key lymphatic markers, VEGFR3, LYVE-1, and Podoplanin, in comparable levels to mature LECs. The differentiated LECs are able to assemble into stable lymphatic vascular networks in vitro, and secrete key lymphangiocrine, reelin.

conclusionOverall, our protocol has broad applications for basic study of lymphatic biology, as well as toward various approaches in lymphatic regeneration and personalized medicine.

Indexed as

Cell DifferentiationEndothelial CellsTranscription FactorsHumansInduced Pluripotent Stem CellsLymphatic VesselsProto-Oncogene Protein c-ets-2ETS2 protein, humanETV2 protein, humanProto-Oncogene Protein c-ets-2Transcription FactorsBiomedical engineeringLymphatic biologyStem cell differentiationTissue engineeringTranscription factorsVascular biology

Identifiers

PMID39197437
PMCPMC11633880

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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.