Open research questions in Pluripotent Stem Cells Research
420 gap statements mined from Pluripotent Stem Cells Research papers in our 7.9M-paper local library, which holds 2,147 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
Further studies are needed to clarify how specific lipid species, FAO-related intermediates, and mitochondrial redox states determine VSMC/PASMC fate in different vascular diseases. The relevance of the BCKDK-BCKDH-BCAA-mTOR pathway to other vascular diseases remains to be established.
Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching · 2026 · DOIIt highlights the need to consider disease-context-specific metabolic patterns. The study aims to address the lack of understanding of how metabolic reprogramming regulates VSMC phenotypic plasticity.
Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching · 2026 · DOIConventional methods for cerebral organoid production are labor-intensive and limited in scalability. There is a need for improved size homogeneity and reproducibility in cerebral organoid production. The relationship between size variability and protein expression in cerebral organoids is not well understood.
ART has transformed clinical practice but still faces modest success rates, poorly defined implantation conditions, and persistent gaps in understanding early human development.
These models are limited by their DNA embryonic age, low neuronal yields, and limited disease pathology.
Huntington’s disease human lateral ganglionic eminence precursors differentiate into functionally mature medium spiny neurons exhibiting pathology · 2026 · DOIDespite sex differences in adult cardiac metabolism, sex effects in hiPSC-CMs remain poorly defined.
Donor sex modulates hiPSC-derived cardiomyocyte metabolic and functional response to fatty acids · 2026 · DOIReprogramming somatic cells to induced pluripotent stem cells (iPSCs) involves transcriptional and epigenomic remodeling, yet how these changes relate along productive and unsuccessful trajectories remains unclear.
For mesenchymal stem cells, clinical benefit has been predominantly observed in early-stage patients with diabetes, and the optimal sources for distinct disease entities warrant further investigation.
Although endoglin (ENG) is traditionally recognized as a coreceptor in TGF‐β signaling, its role in human pluripotent stem cells (hPSCs) remains unexplored.
Endoglin Regulates Pluripotency and Differentiation in Human Embryonic Stem Cells Through Wnt and TGF‐β Signaling Crosstalk · 2026 · DOIIn particular, mitochondrial pyruvate oxidation in pluripotency regulation has not been documented.
Acetyl‐CoA Homeostasis via Mitochondrial Pyruvate Oxidation Governs Survival, Transcriptional Fidelity and Neural Specification in Primed Human Embryonic Stem Cells · 2026 · DOIMany cell lines exhibit remarkable genetic stability, but little is known about the basis of the known variation in genomic integrity amongst different PSC isolates.
Chromosome X dosage modulates development of aneuploidy in genetically diverse mouse embryonic stem cells · 2026 · DOIHowever, the molecular mechanisms regulating the 2-cell-like state in ESCs are not fully understood.
Shugoshin 2A stabilizes heterochromatin complexes to suppress the 2-cell-like state in embryonic stem cells · 2026 · DOIAlthough many transcription factors (TFs) guiding mDAN development have been identified, the details of the underlying regulatory networks remain elusive.
ZFHX4 is necessary for dopaminergic neuron differentiation and controls cell cycle by regulating LIN28A · 2026 · DOIDespite the central role of the nucleus in the cell, it remains unclear what determines nuclear size.
However, the molecular mechanisms that govern fate specification between oral epithelium and surface ectoderm remain poorly understood.
Development of a high-efficiency induction system for embryonic oral epithelium from human pluripotent stem cells · 2026 · DOITranscription factor (TF)-mediated induction of human pluripotent stem cells (PSCs) rapidly generates GABAergic neurons, yet their regional identity remains poorly defined.
Directing GABAergic neuronal identity from human iPSCs through developmental patterning · 2026 · DOICell-based regenerative therapies represent a promising platform for muscular dystrophies, but the role of histocompatibility for muscle engraftment remains poorly defined.
Donor-intrinsic regenerative potential outweighs histocompatibility in iPSC-derived skeletal muscle engraftment in nonhuman primates · 2026 · DOIMicroRNAs from the miR-290 and miR-302 clusters have been shown to greatly increase reprogramming efficiency, but their requirement in the process has not been studied.
The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells · 2025 · DOIMitochondria are crucial for cell fate determination, yet their roles in human pluripotent stem cell (hPSC) fate changes have remained underexplored.
Mitochondrial Pyruvate Carrier Differentially Controls the Self‐Renewal and Differentiation of Human Pluripotent Stem Cells · 2025 · DOIHowever, a role for mitochondrial movement and distribution in pluripotency remains unknown.
Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction · 2025 · DOIThe proteomic analyses were performed on a small number of organoids derived from two iPSC lines. Precise quantification of organoid number during long-term culture in bioreactor tubes remains technically challenging. The CERO 3D system requires specialized equipment and maintenance, which may limit accessibility for some laboratories.
It also highlights the difficulty of maintaining captive populations of many different individual species to address questions in evolutionary molecular physiology.
However, the effects of CRISPR editing and neural differentiation on XCI erosion and how this may confound a real-world analysis of differentially expressed genes (DEGs) are poorly understood.
Female iPSC X chromosome inactivation erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation · 2026 · DOIHarnessing these human stem cell models to devise phenotypic drug discovery platforms can eventually pave the way for innovative therapeutic interventions, particularly in the context of disorders with poorly understood genetic mechanisms and limited therapeutic options.
NEW & NOTEWORTHY Standard iPSC differentiation protocols rely on Matrigel, a basement membrane extract from mouse sarcoma cells that is poorly defined and exhibits significant batch-to-batch variation.
Engineered hydrogel biomaterials facilitate lung progenitor cell differentiation from induced pluripotent stem cells · 2025 · DOI
Most-cited papers in Pluripotent Stem Cells Research
- Embryonic Stem Cell Lines Derived from Human Blastocysts · Science · 1998 · 12,892 citations
- Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells · Science · 2007 · 8,673 citations
- Establishment in culture of pluripotential cells from mouse embryos · Nature · 1981 · 6,741 citations
- Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche · Nature · 2009 · 6,701 citations
- Mammalian Neural Stem Cells · Science · 2000 · 3,844 citations
- Generation of germline-competent induced pluripotent stem cells · Nature · 2007 · 3,614 citations
- The ground state of embryonic stem cell self-renewal · Nature · 2008 · 3,149 citations
- Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene · Nature · 1996 · 2,897 citations
- Organogenesis in a dish: Modeling development and disease using organoid technologies · Science · 2014 · 2,696 citations
- An atlas of active enhancers across human cell types and tissues · Nature · 2014 · 2,521 citations
Most recent work
- Eliminate, Reprogram, and Rebuild · Longevity Horizon · 2026
- Integrated Manufacturing Platform for Cortical Organoids Reveals Early Phosphatase and Prefoldin Dysregulation in MAPT V337M Neurons · bioRxiv · 2026
- Centriole Elimination as a Gateway to a New Differentiation State: A Hypothesis · Longevity Horizon · 2026
- Prevention of transgene silencing during human pluripotent stem cell differentiation · Cell stem cell · 2026
- Two decades of induced pluripotent stem cell research: From discovery to diverse applications · Cell stem cell · 2026
- Anti-aging strategies and ex vivo organ rejuvenation · Cell stem cell · 2026
- Cognitive rejuvenation through partial reprogramming of engram cells · Neuron · 2026
- Brain organoids in environmental neurotoxicology: applications, mechanisms, and future perspectives · Cell Biology and Toxicology · 2026
- Human pluripotent stem cell-derived innate and adaptive immune cells for cancer immunotherapy · Cell stem cell · 2026
- Bridging population and cell: modelling complex diseases with human induced pluripotent stem cells · European Journal of Human Genetics · 2026
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