Kuraoka, K. | Search bioRxiv

bioRxiv2024

Discovering cancer stem-like cells using Spatial transcriptomic analysis: Nuclear factor I X as a novel therapeutic target for gastric cancer

BackgroundGastric cancer (GC) is characterized by significant intratumoral heterogeneity and stem cells presenting as promising therapeutic targets. Despite advancements in spatial transcriptome analysis, unexplored targets for addressing cancer stemness remain unknown. This study aims to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. MethodsSpatial transcriptome analysis was conducted on GC. NFIX expressions correlation with clinicopathological factors and prognosis was assessed through immunostaining in 127 GC cases. Functional analyses in cancer cell lines validated these findings. ResultsSpatial transcriptome analysis stratified GC tissues based on genetic profiles, pinpointing CSC-like cells and further refined the classification to identify and highlight the NFIXs significance, validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. ConclusionsThis study underscores spatial transcriptome analysiss role in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as pivotal. NFIX expression correlates with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.

pathology↗

bioRxiv2024

Differential and temporally dynamic involvement of primate amygdala nuclei in face animacy and reward information processing

Decision-making is influenced by both expected reward and social factors, such as who offered the outcomes. Thus, although a reward might originally be independent from social factors, the two elements are closely related. However, whether and how they are processed separately or conjointly remains unclear. Here, we show that neurons in distinct sub-nuclei of the amygdala encode expected reward and face animacy, which is a vital aspect of face perception. Although these encoding processes are distinct, they rely on partially shared neuronal circuits with characteristic temporal dynamics. Two male macaque monkeys made saccades under different social and reward contexts, created by presenting facial images with independent attributes: animacy (a monkey or cartoon face) and associated reward (large or small). The stimulus image was presented twice per trial: during the initial stimulus encoding (S1) and before saccades were made (S2). A longer gaze duration for eye region of the monkey versus cartoon images indicated more robust social engagement for realistic faces. During S1, a similar number of lateral nucleus neurons encoded either animacy only with a monkey-image preference, reward only with a large-reward preference, or both. Conversely, neurons in the basal and central nuclei primarily encoded reward, preferring large-versus small-reward associated face images. The reward-dependent modulation was continuous after S1, but was more conspicuous during S1 in the basal nucleus and during both S1 and S2 in the central nucleus. This anatomically- and temporally-specific encoding in the amygdala may underlie the computation and integration of face animacy and reward information. Significance StatementReward and social information are closely related but originally independent, as both influence our decision-making. The amygdala has been associated with both reward and social information coding. However, whether and how they are processed separately or conjointly by individual neurons in the amygdala remains unclear. We found that neurons in the lateral and basal nuclei encoded face animacy, which is an important aspect of social information, and reward, respectively, during sensory processing. Neurons in the central nucleus encoded reward information during the execution phase. This provides new clarity regarding the mechanisms of separate or integrated social and reward information processing within the amygdala.

neuroscience↗