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Biology subjects

Chung, B. K.

Publications and source records attributed to Chung, B. K..

3 recordsLinked to original sources

Co-aggregation of pre-conditioned cell populations drives controlled lineage bias and formation of gut tube-like structures in human stem cell-based embryo models

Human stem cell-based embryo models (hSCBEMs) provide a powerful platform for investigating post-implantation human embryo development but are frequently hindered by variability in growth and morphogenesis as well as incomplete lineage representations. Here, we present a modular hSCBEM aggregation approach based on co-aggregation of differentially pre-conditioned, human pluripotent stem cell derived cells pools. Using this strategy, we generated hSCBEM with consistent morphotypes that targets robust morphogenesis of gut tube-like structures in combination with mesodermal lineages. Our findings demonstrate that co-aggregating defined cellular heterogeneity represents a versatile approach to specifically guide self-organization in hSCBEMs while improving reproducibility and developmental fidelity. The approach provides a robust platform for supervised morphogenesis in hSCBEMs.

developmental biology↗

Reconstituting epiblast-extraembryonic endoderm interactions restores anterior-ventral patterning in stem cell-based embryo models.

During mammalian embryogenesis, reciprocal interactions between the epiblast and extraembryonic endoderm are critical for germ layer specification and body plan development during gastrulation. Gastruloids recapitulate aspects of gastrulation in the absence of extraembryonic cues, resulting in a predominantly posteriorized and dorsalized phenotype with a limited lineage diversity. Here, we establish a modular co-aggregation ("aggregoid") strategy that spatially couples embryonic and extraembryonic endoderm-like cells to reconstruct key interactions in vitro. This drives self-organized anterior-ventral patterning together with the emergence of node- and notochord-like structures, enriched endodermal populations, and increased mesodermal diversity, including cardiopharyngeal lineages and vascular endothelium. Our findings demonstrate that modular engineering of lineage interactions can direct self-organized patterning in stem-cell-based embryo models and provide a versatile framework for generating defined morphotypes.

developmental biology↗

Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies

A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19- CD45- (age>20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19-CD45+ (age>10 years) and short-lived CD19+CD45+ (age<2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.

immunology↗