Biology subjects

Wang, X.-M.

Publications and source records attributed to Wang, X.-M..

3 recordsLinked to original sources

bioRxiv2026

P-glycoprotein exofection between fetal and maternal cells as a mechanism of intercellular material transfer at the feto maternal interface

Cells can recover lost protein functions through a process we term exofection, in which extracellular vesicles deliver functional molecular cargo to recipient cells and transiently reprogram their activity. Here we show that exosomes derived from fetal chorion trophoblast cells (CTCs) restore P-glycoprotein (P-gp) efflux transporter function in inflammation-impaired maternal decidual cells (DECs) at the feto-maternal interface. CTCs maintain high P-gp expression under inflammatory stress, whereas DECs exhibit marked downregulation of transporter genes and proteins. Proteomic analysis revealed that CTC-derived exosomes package P-gp as a stable cargo that enters DECs through clathrin- and heparan sulfate-dependent uptake pathways. Delivery of CTC exosomes reinstated P-gp abundance and efflux capacity in LPS-stimulated or P-gp-deficient DECs, as shown by calcein efflux and immunofluorescence assays. In pregnant P-gp knockout mice, exosome treatment restored systemic clearance of the P-gp substrate tacrolimus and improved pharmacokinetic parameters. These findings establish exofection as a naturally occurring mechanism of transporter rescue at the feto-maternal interface, where fetal exosomes compensate for inflammation-induced maternal loss of efflux capacity. By restoring P-gp-mediated barrier function, exofection provides a protective strategy that limits the accumulation of xenobiotics and cytokines in maternal tissues and safeguards the fetus. This work reveals a previously unrecognized form of intercellular communication with broad implications for fetal protection, placental biology, cellular engineering, and the delivery of therapeutic proteins. One Sentence SummaryExofection is identified as a novel mechanism of transient cellular engineering via exosome-mediated functional protein delivery between cells.

developmental biology↗

bioRxiv2025

Harnessing landscape genomics to evaluate genomic vulnerability and future climate resilience in an East Asia perennial

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions, bolstering population resilience, and shaping germplasm conservation strategies tailored to specific species. Here we integrated population genomics and landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation to capture the majority of existing adaptive diversity. Our analysis unveiled that the species complex comprised two distinct genetic clusters, exhibiting differential climate adaptation and genomic vulnerabilities across its distribution range. We also determined that the species range could be subdivided into three distinct seed zones, with varying sample requirements per seed zone corresponding to differed conservation efforts. Overall, our findings provide a genome-wide perspective on climate adaptation and valuable insights into germplasm conservation strategies aimed at enhancing population resilience in future climates, serving as a blueprint for restoration plans of other vulnerable species.

evolutionary biology↗

bioRxiv2024

CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development--either alone, or in the context of other genetic alterations--and whether CDK12-mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate. Allograft-based CRISPR screening demonstrated that Cdk12 loss is positively associated with Trp53 inactivation but negatively associated with Pten inactivation--akin to what is observed in human mCRPC. Consistent with this, ablation of Cdk12 in prostate organoids with concurrent Trp53 loss promotes their proliferation and ability to form tumors in mice, while Cdk12 knockout in the Pten-null prostate cancer mouse model abrogates tumor growth. Bigenic Cdk12 and Trp53 loss allografts represent a new syngeneic model for the study of androgen receptor (AR)-positive, luminal prostate cancer. Notably, Cdk12/Trp53 loss prostate tumors are sensitive to immune checkpoint blockade. Cdk12-null organoids (either with or without Trp53 co-ablation) and patient-derived xenografts from tumors with CDK12 inactivation are highly sensitive to inhibition or degradation of its paralog kinase, CDK13. Together, these data identify CDK12 as a bona fide tumor suppressor gene with impact on tumor progression and lends support to paralog-based synthetic lethality as a promising strategy for treating CDK12-mutant mCRPC.

cancer biology↗