Biology subjects

Hwang, Y. Y.

Publications and source records attributed to Hwang, Y. Y..

2 recordsLinked to original sources

bioRxiv2025

Direct contact between iPSC-derived macrophages and hepatocytes drives reciprocal acquisition of Kupffer cell identity and hepatocyte maturation

Hepatic macrophages play central roles in liver homeostasis, injury, and immune-mediated hepatotoxicity through dynamic crosstalk with hepatocytes. While monocyte-derived macrophages have been widely used in vitro, they do not fully recapitulate the biology of liver-resident Kupffer cells (KCs), which are embryonically derived and maintained locally. Recent advances suggest that induced pluripotent stem cell (iPSC)-derived macrophages (iMacs) more closely resemble embryonic macrophages and may therefore serve as a relevant platform to model KC biology. Here, we developed a human iPSC-based co-culture system by combining iMacs with iPSC-derived hepatocytes (iHeps) derived from the same donor, enabling direct cell-cell interactions. We hypothesized that such interactions would both enhance hepatocyte maturation and promote KC-like differentiation of iMacs. Indeed, co-culture induced KC-like phenotypes in iMacs and improved functional maturation of iHeps, highlighting the importance of bidirectional cellular communication. Comparative analyses with iMacs cultured in hepatocyte-conditioned media revealed that direct contact provides additional signals beyond soluble factors in driving hepatic macrophage specialization. Functionally, this co-culture system demonstrated improved physiological relevance, particularly in modeling immune-mediated drug responses, as evidenced by enhanced cytokine production profiles upon exposure to a panel of test compounds. Overall, this study establishes a novel human iPSC-derived platform that captures key aspects of hepatocyte-macrophage crosstalk, providing a more physiologically relevant model to investigate liver biology and assess immune-mediated drug toxicity.

immunology↗

bioRxiv2024

Single-cell analysis of human diversity in circulating immune cells

Lack of diversity and proportionate representation in genomics datasets and databases contributes to inequity in healthcare outcomes globally1,2. The relationships of human diversity with biological and biomedical phenotypes are pervasive3, yet remain understudied, particularly in a single-cell genomics context. Here we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA-sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 healthy donors and 6 controls, spanning 7 population groups across 5 countries. AIDA is one of the largest healthy blood datasets in terms of number of cells, and also the most diverse in terms of number of population groups. Though population groups are frequently compared at the continental level, we identified a pervasive impact of sub-continental diversity on cellular and molecular properties of immune cells. These included cell populations and genes implicated in disease risk and pathogenesis as well as those relevant for diagnostics. We detected single-cell signatures of human diversity not apparent at the level of cell types, as well as modulation of the effects of age and sex by self-reported ethnicity. We discovered functional genetic variants influencing cell type-specific gene expression, including context-dependent effects, which were under-represented in analyses of non-Asian population groups, and which helped contextualise disease-associated variants. We validated our findings using multiple independent datasets and cohorts. AIDA provides fundamental insights into the relationships of human diversity with immune cell phenotypes, enables analyses of multi-ancestry disease datasets, and facilitates the development of precision medicine efforts in Asia and beyond.

genomics↗