Biochemistry, Genetics and Molecular Biology · Research topic

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 · DOI
  • It 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 · DOI
  • Conventional 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.

    A refined protocol for the large-scale production of high-quality cerebral organoids · 2026 · DOI
  • ART has transformed clinical practice but still faces modest success rates, poorly defined implantation conditions, and persistent gaps in understanding early human development.

    Stem cell-based embryo models as a tool for reproductive biology · 2026 · DOI
  • 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 · DOI
  • Despite 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 · DOI
  • Reprogramming 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.

    Epigenomic heterogeneity and spatial organization during human reprogramming · 2026 · DOI
  • 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.

    Stem cell therapy for endocrine and metabolic disorders · 2026 · DOI
  • 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 · DOI
  • In 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 · DOI
  • Many 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 · DOI
  • However, 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 · DOI
  • Although 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 · DOI
  • Despite the central role of the nucleus in the cell, it remains unclear what determines nuclear size.

    ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37 · 2026 · DOI
  • 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 · DOI
  • Transcription 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 · DOI
  • Cell-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 · DOI
  • MicroRNAs 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 · DOI
  • Mitochondria 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 · DOI
  • However, a role for mitochondrial movement and distribution in pluripotency remains unknown.

    Perinuclear mitochondrial clustering for mesenchymal-to-epithelial transition in pluripotency induction · 2025 · DOI
  • The 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.

    A refined protocol for the large-scale production of high-quality cerebral organoids · 2026 · DOI
  • It also highlights the difficulty of maintaining captive populations of many different individual species to address questions in evolutionary molecular physiology.

    Primary Cell Culture as a Model System for Evolutionary Molecular Physiology · 2024 · DOI
  • 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 · DOI
  • Harnessing 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.

    Neuronal branching in stem cell models of mitochondrial and neurological diseases · 2025 · DOI
  • 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

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Related topics in Biochemistry, Genetics and Molecular Biology

Open questions raised by papers listed on this page include: (1) 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 (“Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic…”, 2026); (2) There is a need for improved size homogeneity and reproducibility in cerebral organoid production (“A refined protocol for the large-scale production of high-quality cerebral…”, 2026); (3) Reprogramming 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 (“Epigenomic heterogeneity and spatial organization during human reprogramming”, 2026); (4) 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…”, 2026); (5) Many 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…”, 2026). 420 gap statements have been mined from Pluripotent Stem Cells Research papers in our 7.9M-paper local library, which holds 2,147 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. 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, so you can read the original claim in context.

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