ArticleStem cells (Dayton, Ohio)2016
Molecular Analysis of Neutrophil Differentiation from Human Induced Pluripotent Stem Cells Delineates the Kinetics of Key Regulators of Hematopoiesis.
Article in Stem cells (Dayton, Ohio), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
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.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Impact of Air Pollution on Our Epigenome: How Far Is the Evidence? (A Systematic Review).Current environmental health reports · 2018Pooled it
- CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Lipid droplet profiling during neutrophil differentiation by stimulated Raman scattering microscopy.Biotechnology progress · 2026Article
- Modeling myeloid cell development in health and disease using induced pluripotent stem cells.Frontiers in immunology · 2026Review
- Human induced pluripotent stem cells derived neutrophils display strong anti-microbial potencies.Cell regeneration (London, England) · 2025Article
- Forward programming of hPSCs to neutrophils using chemically defined media.Stem cell research & therapy · 2025Article
- Neutrophils cultured ex vivo from CD34Journal of translational medicine · 2024Article
- Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges.Cell regeneration (London, England) · 2023Review
- Review
- Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy.Cell reports · 2022Article
- Cell Fate Reprogramming in the Era of Cancer Immunotherapy.Frontiers in immunology · 2021Review
- The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development.Frontiers in immunology · 2021Article
- LPS and IL-8 activated umbilical cord blood-derived neutrophils inhibit the progression of ovarian cancer.Journal of Cancer · 2020Article
- Effective and Rapid Generation of Functional Neutrophils from Induced Pluripotent Stem Cells Using ETV2-Modified mRNA.Stem cell reports · 2019Article
- Article
- Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators.Current genomics · 2019Review
- Long Non-coding RNAs in Myeloid Malignancies.Frontiers in oncology · 2019Review
- Tuning the interactions between chiral plasmonic films and living cells.Nature communications · 2017Article
- RARα2 and PML-RAR similarities in the control of basal and retinoic acid induced myeloid maturation of acute myeloid leukemia cells.Oncotarget · 2017Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a four-stage differentiation protocol involving: embryoid body (EB) formation (stage-1); EB culture with hematopoietic cytokines (stage-2); HSPC expansion (stage-3); and neutrophil maturation (stage-4). CD34(+) CD45(-) putative hemogenic endothelial cells were observed in stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34(+) CD45(-) cells generated CD34(+) CD45(+) HSPCs that produced hematopoietic CFUs. Mid-stage-3 CD34(+) CD45(+) HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBPα, and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune-deficient mice. Mid-stage-3 CD34(-) CD45(+) cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBPɛ expression were observed, with 25%-65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular signatures that may serve as a guide for enhancing iPSC hematopoiesis. Stem Cells 2016;34:1513-1526.
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Registered trials
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.