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Mo Li

Publications and source records attributed to Mo Li.

2 recordsLinked to original sources
PubMed2026

In vivo labeling-based proteomic analysis of early follicle oocytes and cisplatin-induced alterations in mice.

A systematic proteomic profile of oocytes from early-stage follicles, particularly primordial follicles, is critical to protect female reproductive capacity in the context of chemotherapy, yet progress has been hindered by the rarity of oocyte samples and technical challenges associated with oocyte isolation. In this study, we generated in vivo oocyte protein labeling APEX fluorescent mice. With these mice, we reconstructed the ovary in 3D, enabling precise quantification of follicles and identified 2772 proteins and 2878 gene transcripts in oocytes predominantly from primordial follicles. Proteomic shifts of short-time cisplatin treatment revealed that many altered proteins were involved in DNA damage repair and histone modification. Notably, simultaneous application of cisplatin and EZH2's inhibitor, GSK126, relieved cisplatin-induced oocyte developmental defects. Our study provides a systematic proteomic characterization of oocytes predominantly from primordial follicles in female mice, and reveals dynamic proteome shifts in response to chemotherapeutic agents, laying the foundation for targeted fertility-preserving strategies.

Animals↗
PubMed2026

A single small molecule-based human embryo model reveals V-ATPase requirement in mammalian blastocyst cavitation.

Human naïve pluripotent stem cells (nPSCs) can be induced by various combinations of signaling factors to generate blastocyst-like structures, termed blastoids. Despite rapid progress in human blastoid models, their potential to uncover fundamental mechanisms of early human development remains limited, leaving key morphogenetic processes poorly understood. Here, we describe a simple and robust system in which dimethyl sulfoxide (DMSO) alone induces blastoid formation from human nPSCs. This model recapitulates key pre- and post-implantation features and exhibits enhanced polar trophectoderm (TE) organization, more efficient attachment within an implantation-relevant window, improved epiblast lumenogenesis associated with amniotic cavity formation, and more robust, sustained expansion of embryonic lineages following attachment. Using this system, we reveal a previously unrecognized mechanism underlying TE cavitation and identify lysosome-associated genes - particularly subunits of the proton pump V-ATPase - as essential regulators of blastoid cavitation. DMSO treatment upregulates key V-ATPase subunits (ATP6V0A4 and ATP6V1B1), which are also enriched in the TE of human embryos. Genetic or pharmacological inhibition of V-ATPase activity disrupts lysosomal acidification, blocks intracellular vacuole formation, and impairs blastoid cavitation, whereas overexpression of V-ATPase subunits rescues this phenotype. Furthermore, genetic and pharmacological perturbations of V-ATPase function significantly compromise cavitation in both mouse and human blastocysts. Finally, DMSO treatment induces membrane biomechanical changes characteristic of early embryonic development, suggesting a mode of action distinct from conventional small-molecule, signaling pathway-based induction strategies. This simple DMSO-based blastoid model recapitulates key aspects of human blastocyst development and reveals a conserved requirement for V-ATPase-mediated lysosomal acidification during early mammalian embryogenesis.

Humans↗