The advent of single-cell technology has transformed our ability to investigate disease evolution at a cellular level, accelerating our understanding of complex mechanisms and enabling more effective treatment strategies. To date, MGI’s single-cell platform has powered 295 SCI publications, including 14 high-impact studies in Cell, Nature, and Science.
This momentum continued into January 2026, with 12 new SCI studies leveraging MGI’s single-cell technology. While these papers span diverse fields, most focus on the intersection of disease mechanisms and therapeutic interventions. Here, we highlight two significant studies on diabetes and kidney stones, demonstrating how MGI’s single-cell approach helps reveal the profound impact of microenvironmental changes on cellular behaviour.
Study I:
Zinc Accumulation-Induced Integrated Stress Response Triggers β-Cell Identity Loss
Journal: Cell Research, IF 25.9
Biological Specimens: hESC-derived pancreatic β-cells
Methods: Human embryonic stem cell (hESC)-derived islet models, FACS, ChIP-qPCR, scRNA-seq, Western blot, in vivo murine drug administration, and functional evaluation
Research Background
A major challenge in diabetes cell therapy is the inability of transplanted pancreatic β-cells to survive long-term and maintain stable function within the pathological diabetic microenvironment. As the sole insulin-producing cells in humans, β-cell dysfunction is a key factor in type 2 diabetes (T2D) pathogenesis. Clinical studies show that T2D patients experience a 25%-60% reduction in β-cell mass compared to healthy individuals. Evidence indicates that this depletion results not from cell death but from β-cell identity loss, where chronic diabetic stress or genetic defects cause mature β-cells to dedifferentiate into progenitor-like states or transdifferentiate into other pancreatic endocrine cells (e.g., α-cells or INS⁺GCG⁺ bihormonal cells). This phenomenon, consistently observed in mouse models, non-human primates, and T2D patients, manifests as decreased β-cell numbers alongside increased α-cell and double-positive cell populations.
Emerging research implicates genetic susceptibility, oxidative stress, and ER stress in driving β-cell identity loss, potentially through dysregulation of key transcription factors (e.g., FOXO1, PDX1, NKX6.1) or aberrant activation of α-cell-specific factors such as ARX. This study reveals a novel mechanism: zinc accumulation triggers β-cell dedifferentiation via the integrated stress response (ISR), offering new insights for therapeutic intervention.
Highlights
- In both T2D patients and mouse islets, zinc accumulation activates the integrated stress response (ISR), elevating ATF4 expression, which in turn activates the α-cell-specific transcription factor ARX, driving β-to-α cell transdifferentiation.
- Both high-glucose conditions and zinc ionophore treatment can lead to a reduction in β-cell proportion and an increase in α/bihormonal cell populations.
- Transplanted SC-β cells in diabetic animal models similarly exhibited identity loss, whereas genetic knockout or chemical inhibition of zinc accumulation effectively preserved β-cell identity and improved glycemic control.
Study II:
Journal: Advanced Functional Materials, IF 19.0
Biological Specimens: Mouse kidney
Methods: Molecular docking iterative design, microwave synthesis of Ce-CDs, fluorescence spectroscopy, antioxidant assays, scRNA-seq, and in vitro/in vivo functional evaluation in mouse models
Research Background
Kidney stones (KS) are among the most common urological disorders, with high incidence and recurrence rates. Patients may experience complications ranging from acute pain and renal impairment to potentially life-threatening systemic infections. Although citrate-based medications are used clinically to reduce stone formation, their limited efficacy and notable side effects highlight the urgent need for more effective therapeutic strategies.
Pathogenesis of KS is closely linked to oxidative stress and ferroptosis in renal tubular epithelial cells within the kidney microenvironment. The pentacyclic triterpenoid celastrol (Cel) shows therapeutic potential due to its anti-inflammatory and antioxidant properties, but its narrow therapeutic window and poor targeting have hindered clinical application.
To overcome these limitations, this study employed molecular docking and structure-activity relationship optimisation to develop a “drug-excipient integrated” cerium (Ce)-doped glutathione carbon dot (Ce-CDs) for targeted Cel delivery. This nanomedicine, Ce-CDs@Cel, not only directly erodes kidney stones but also inhibits ferroptosis via upregulation of the Slc7a11/GPX4 pathway, while simultaneously remodelling the renal microenvironment, offering a novel approach for KS treatment.
Research Highlights
- An iterative optimisation strategy was used, starting with citric acid as the precursor and combining molecular docking, microwave synthesis, and performance screening to construct cerium (Ce)-doped glutathione carbon dot nanocarriers.
- The nanodrug Ce-CDs@Cel demonstrated excellent biocompatibility and significant therapeutic efficacy both in vitro and in vivo, representing a promising candidate for precision treatment of kidney stones.
- This study achieved the first triple synergistic effects: direct stone dissolution, ferroptosis inhibition, and renal microenvironment remodelling, overcoming the limitations of traditional single-mechanism therapies.
- Ce-CDs@Cel inhibits ferroptosis via upregulation of the Slc7a11/GPX4 pathway, offering new insights into kidney stone pathogenesis.
In addition to the mechanistic and therapeutic studies on diabetes and kidney stones using single-cell sequencing technology, six other publications examined the underlying mechanisms of colorectal cancer, postpartum depression, acute kidney injury, ulcerative colitis, sepsis-associated acute lung injury, and ovarian cancer.
For further information on these publications, please contact MGI-service@mgi-tech.com
