Biology subjects

Yang, M.-T.

Publications and source records attributed to Yang, M.-T..

4 recordsLinked to original sources

bioRxiv2025

Single-cell lineage tracing identifies hemogenic endothelial cells in the adult mouse bone marrow

During mouse development, hematopoietic stem and progenitor cells (HSPC) originate from hemogenic endothelial cells (ECs) through a process of endothelial-to-hematopoietic transition. These HSPC are thought to fully sustain adult hematopoiesis. However, it remains unknown whether adult ECs retain hemogenic potential. Here we used in vivo genetic lineage tracking at population and single-cell (sc) levels, scRNA sequencing, and bone marrow transplantation to detect hemogenic ECs in adult mice. We identify and characterize bone marrow-resident, adult Cdh5/VE-Cadherin+ ECs that produce hematopoietic cell-progeny in vitro and in mice. These adult hemogenic ECs and their hematopoietic cell progeny give rise to hematopoietic cells following adoptive transfer into adult mice. Furthermore, blood cells generated from adult and developmental ECs comparably home to peripheral tissues, where they similarly contribute to inflammatory responses. Thus, our results identify previously unrecognized bone marrow-derived adult hemogenic ECs that generate HSPC and functional mature blood cells.

cell biology↗

bioRxiv2025

Integrated metagenome-resolved profiling of the resistome, virulome, and mobilome in the gut microbiota of wild birds

Wild birds, with their extensive geographic distributions and high mobility, are increasingly recognized as important players in the dissemination of antimicrobial resistance. Their gut microbiota, shaped by exposure to diverse environments, may act as both reservoirs and vectors of antibiotic resistance genes (ARGs), virulence factor genes (VFGs), and mobile genetic elements (MGEs). In this study, we reconstructed 2,516 high-quality metagenome-assembled genomes (MAGs) from 718 gut metagenomes of wild birds to comprehensively profile their resistome and virulome. We identified 5,596 ARG-encoding proteins across 389 distinct ARG types, with multidrug resistance emerging as the most dominant category. Escherichia coli was the principal carrier of ARGs, and genes conferring resistance to elfamycin antibiotics via target alteration were notably widespread--indicating persistent antibiotic selection pressures in avian habitats. Co-occurrence analyses revealed extensive genetic linkage between ARGs, VFGs, and MGEs. Critically, we detected 25 ARG-MGE co-localization events within 5-kilobase genomic regions, highlighting a strong potential for horizontal gene transfer and accelerated resistance dissemination within microbial communities. Of particular concern was the detection of the tetX1 gene--conferring resistance to tigecycline, a last-resort antibiotic--in the gut microbiota of Chroicocephalus ridibundus and Cygnus cygnus. This finding strongly implicates anthropogenic pollution in the spread of clinically relevant ARGs into wildlife and emphasizes the risk of environmental transmission to other hosts, including humans. These results underscore the critical ecological role of wild birds in the global antimicrobial resistance network. As both reservoirs and potential vectors of ARGs, they represent a significant but under-monitored interface between environmental and clinical resistance pathways. Enhanced surveillance and mitigation strategies targeting wildlife are urgently needed to curb the environmental propagation of antimicrobial resistance.

microbiology↗

bioRxiv2023

Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium

Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium.

immunology↗

bioRxiv2022

Bone marrow hemogenic endothelial cells contribute multilineage hematopoietic progenitors in adult mice

During development, hematopoietic stem/progenitor cells (HSPCs) originate from a subset of hemogenic endothelial cells (ECs) through a process of endothelial-to-hematopoietic transition (EHT). This process is temporally restricted to short developmental windows and generates HSPC with distinct capabilities for hematopoiesis. Although it is generally thought that adult hematopoiesis is sustained by HSCs derived from hemogenic endothelium during development, some observations point to EHT persistence in the late fetus/perinatally. Here we use lineage tracking and bioinformatics analysis to assess the presence of hemogenic endothelial cells in the adult mouse. Our analysis identifies a subset of bone marrow-resident adult endothelial cells, characterized by the expression of VE-Cadherin and the transcription factor RUNX1, that produce CD45+ hematopoietic cells. This EHT generates hematopoietic progenitors, and mature myeloid and lymphoid cells in the adult mouse. Our results reveal the identification of a distinct source of adult blood.

cell biology↗