GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Mechanisms
  GSE316208Mus musculus12 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

  单细胞空间转录组扰动筛选
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq MC38]
  GSE341712Mus musculus12 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  单细胞空间转录组