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Zhao, Z.

Publications and source records attributed to Zhao, Z..

2 recordsLinked to original sources

Living multicellular systems induce decodable spatial patterns in bacterial collectives

Living systems continuously modify their environments through chemical, mechanical, metabolic and bioelectrical activity. Whether a presence of a multicellular system can be encoded into the emergent spatial organization of another living collective in a distributed and decodable way is unknown. Here we show that motile Bacillus subtilis populations reorganize their spatial and ionic collective states in response to nearby Xenopus embryos and Xenobots. The bacteria in a liquid culture formed autonomous motility-dependent patterns that were redirected by living targets into attraction halos, which tracked target position at a distance. Extracellular levels of potassium amplified attraction, altered local potassium dynamics, and coupled target presence to global pattern complexity. Self-supervised machine learning further identified distributed bacterial spatial signatures predictive of Xenopus embryo vs. Xenobot presence at a distance from the target. Together, these findings suggest that bacterial collectives can encode information about the state of other biota in their environment, revealing a previously unrecognized form of inter-kingdom interaction between living morphogenetic systems.

systems biology

POU2AF2/OCA-T1 coactivates POU2F2 and defines a lineage-specific dependency in diffuse large B-cell lymphoma

Lineage-restricted transcriptional programs establish cell identity and can create selective dependencies in cancer. Here, we identify POU2AF2, encoding the transcriptional co-activator OCA-T1, as a critical lineage-specific dependency in a subset of diffuse large B-cell lymphoma (DLBCL). Pan-cancer dependency analyses and patient cohorts reveal elevated POU2AF2 expression in genetically aggressive DLBCL, where its depletion markedly suppresses tumor growth in vitro and in vivo. Mechanistically, POU2AF2 cooperates with the B-cell lineage-defining transcription factor POU2F2 (OCT2) to activate lymphocyte activation gene programs through direct chromatin engagement, thereby sustaining malignant transcriptional networks. We further identified a key epigenetic regulatory axis composed of the lineage-specific transcription factor TCF3 and the histone methyltransferase SET1A-COMPASS that drives POU2AF2 expression downstream of B-cell receptor signaling. Single-cell transcriptomic analysis reveals that POU2AF2 marks and sustains an innate-like B1 B-cell population in vivo, a candidate cell of origin for lymphoma. Together, these findings define a lineage-restricted POU2AF2/POU2F2 transcriptional module, controlled by a TCF3/SET1A epigenetic network, that sustains both innate-like B-cell identity and malignant fitness in DLBCL. Our study uncovers a previously unrecognized lineage-specific transcriptional dependency and highlights POU2AF2 and its associated regulatory circuitry as potential therapeutic targets in aggressive B-cell malignancies.

cell biology