ArticleStem cells (Dayton, Ohio)2023
Modulation of WNT, Activin/Nodal, and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation.
Article in Stem cells (Dayton, Ohio), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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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.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Dose-resolved control of somatic reprogramming by Rora.Stem cell reports · 2026Article
- Culturing Potential: advances in ex vivo cell culture systems for haematopoietic cell-based regenerative therapies.Regenerative therapy · 2025Review
- Cellular and molecular targets in β-Thalassemia: advances in iron Regulation, Erythropoiesis, and Gene-Based therapies.Functional & integrative genomics · 2025Review
- Purine metabolism in bone marrow microenvironment inhibits hematopoietic stem cell differentiation under microgravity.Stem cell research & therapy · 2025Article
- Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer.Cell stem cell · 2024Article
- Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.Frontiers in molecular biosciences · 2024Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human-induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation, and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal, and MAPK signaling pathways by stage-specific addition of small-molecule regulators CHIR99021, SB431542, and LY294002, respectively, and measured the impact on hematoendothelial formation in culture. Manipulation of these pathways provided a synergy sufficient to enhance formation of arterial hemogenic endothelium (HE) relative to control culture conditions. Importantly, this approach significantly increased production of human HSPCs with self-renewal and multilineage differentiation properties, as well as phenotypic and molecular evidence of progressive maturation in culture. Together, these findings provide a stepwise improvement in human iPSC differentiation protocols and offer a framework for manipulating intrinsic cellular cues to enable de novo generation of human HSPCs with functionality in vivo.
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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 Socratic graph.