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Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions. While GATA4-mediated ES-to-iXEN conversion was rapid and nearly deterministic, OCT4-, KLF4-, and SOX2-induced XEN-to-induced pluripotent stem (iPS) reprogramming progressed with diminished efficiency and kinetics. A dominant PrE transcriptional program, safeguarded by GATA4, alongside elevated chromatin accessibility and reduced DNA methylation of the EPI underscored the differential plasticities of the two states. Mapping in vitro to embryo trajectories tracked reprogramming cells in either direction along EPI and PrE in vivo states, without transitioning through the ICM.
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http://dx.doi.org/10.1016/j.devcel.2024.11.022 | DOI Listing |
Biology (Basel)
August 2025
Department of Oral Biology, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.
The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood-retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD).
View Article and Find Full Text PDFMedComm (2020)
September 2025
Department of Biochemistry and Molecular Biology, School of Medicine, Nanjing University of Chinese Medicine, No.138 Xianlin Avenue Nanjing University of Chinese Medicine Nanjing China.
Tumor-associated macrophages (TAMs) are prominent constituents of solid tumors, and their prevalence is often associated with poor clinical outcomes. These highly adaptable immune cells undergo dynamic functional changes within the immunosuppressive tumor microenvironment (TME), engaging in reciprocal interactions with malignant cells. This bidirectional communication facilitates concurrent phenotypic transformation: tumor cells shift toward invasive mesenchymal states, whereas TAMs develop immunosuppressive, pro-tumorigenic traits.
View Article and Find Full Text PDFJ Extracell Vesicles
September 2025
State Key Laboratory of Metabolism and Regulation in Complex Organisms, Hubei Provincial Research Center for Basic Biological Sciences, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, China.
Tumour progression depends on the bidirectional interactions between cancer and stroma in the heterogeneous tumour microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumour survival under starvation is poorly defined. Here, we identify cancer cells selectively secrete miR-33a with the assistance of aconitase 1 (ACO1), an iron-responsive RNA binding protein, under glucose starvation and lower iron level, which affiliates the binding capability of miR-33a and ACO1.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Background: Colorectal cancer (CRC) represents a significant global health challenge. Gut microbiota imbalance and abnormal chromatin modifications play critical roles in the progression of CRC. However, the mechanisms by which they exert their influences, particularly the involvement of ()-mediated post-translational modifications (PTMs), remain inadequately understood.
View Article and Find Full Text PDFVirulence
December 2025
Jiamusi University of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China.
Viral particles and proteins released during infection profoundly reshape the cellular microenvironment by disrupting host signaling, triggering inflammation, and modulating immune responses. Glucose metabolism, a critical hub for energy production and biosynthesis, is highly susceptible to viral reprogramming. This review summarizes recent findings showing that diverse viruses, including influenza virus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and enteroviruses, manipulate glucose metabolic pathways to promote replication and evade immune surveillance.
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