Biology subjects

Domagala, M.

Publications and source records attributed to Domagala, M..

5 recordsLinked to original sources

bioRxiv2025

Attention modulates hippocampal sharp-wave ripples in humans

Hippocampal sharp-wave ripples (SWRs) are high-frequency events critical for memory consolidation, typically studied during sleep and quiet wakefulness. Emerging evidence suggests that SWRs also occur during active behavior, yet their role in awake cognition remains unclear. Here, we demonstrate that changes in sustained attention modulate both the occurrence of SWRs and their temporal alignment to ongoing hippocampal oscillations. Using intracranial EEG recordings from epilepsy patients performing a sustained attention to response task (SART), we first identified attentional states based on behavioral variability and subjective reports. Next, we observed that SWRs were more frequent during high-attention periods, despite the absence of memory demands. Importantly, SWRs during low-attention periods showed higher phase synchrony with low-frequency oscillations (theta to lower beta) indicating increased endogenous coordination of SWRs under low attentional focus. These findings show that SWRs are dynamically regulated by attentional engagement, supporting a broader role for ripples in active cognitive processing.

neuroscience↗

bioRxiv2025

Time-series RNA-Seq and data-driven network inference unveil dynamics of cell activation, survival and crosstalk in Chronic Lymphocytic Leukaemia in vitro models

How do cancer cells respond to their environment, and what are the key regulators behind their behaviour? While immune cell reprogramming in the tumour microenvironment (TME) has been extensively studied, the dynamic regulatory changes within cancer cells in response to interactions with immune cells remain poorly understood. In Chronic Lymphocytic Leukaemia (CLL), this knowledge gap limits our ability to fully grasp the disease progression and to design effective, personalised interventions. To tackle this, we combine time-series transcriptomics with data-driven gene regulatory network (GRN) inference to uncover the temporal regulatory mechanisms driving CLL cell behaviour within a reconstituted in vitro TME. Using cultures of peripheral blood from CLL patients or of purified patient-derived CLL cells, we profile gene expression across five time points spanning 14 days under these experimental conditions. By inferring GRNs from transcription factor activity, we capture patient-specific and temporally resolved regulatory interactions that highlight how immune signals shape cancer cell phenotypic changes. Our network analysis reveals distinct gene modules associated with critical processes such as cytokine signalling, metabolic reprogramming and differentiation, hallmarks of immune-cancer cell interaction. Intriguingly, we found that while the presence of immune cells in the environment significantly alters CLL cell activation, their survival trajectories are predominantly governed by intrinsic features. This study not only offers mechanistic insights into how immune cell presence influences CLL cell fate but also presents a robust computational framework for integrating time-series transcriptomics with GRN inference, which can then be used to study the long-term behaviour of the CLL cells through dynamical modelling.

systems biology↗

bioRxiv2025

Trogocytosis-mediated transfer of FOLR2 from Nurse-like cells to CLL cells is linked to their activation and proliferation

Communication with the lymphoid microenvironment is crucial for survival and proliferation of neoplastic B cells in chronic lymphocytic leukemia (CLL). In this study, we examined nurse-like cells (NLCs), CLL-specific macrophages, strongly implicated in CLL pathogenesis, and their interaction with leukemic cells. Using primary patient cells, we demonstrated that NLCs express high levels of folate receptor beta (FOLR2), which correlates with increased survival of cancer cells in vitro. Furthermore, we discovered that CLL cells acquire functional FOLR2 from NLCs via trogocytosis, enhancing their folate uptake. By mimicking the CLL microenvironment with soluble factors, CD40L and IL-15, we observed a strong NLC-dependent CLL cell activation and proliferation. Moreover, we linked this phenomenon with trogocytosis, by demonstrating that FOLR2+ CLL cells are the predominant population of actively cycling cancer cells. By multiplex immunofluorescence analysis of CLL patient lymph nodes, we confirmed the presence of FOLR2 NLCs, and observed their enrichment in more aggressive and proliferative CLL cases. Finally, we detected FOLR2 cancer cells, providing evidence of trogocytosis in situ. Taken together, we propose FOLR2 as a novel marker of protective NLCs, and highlight the importance of trogocytosis in improved CLL cell adaptation, including NLC-mediated activation and proliferation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=58 SRC="FIGDIR/small/630890v3_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1cde6d6org.highwire.dtl.DTLVardef@ee0f67org.highwire.dtl.DTLVardef@1355cb3org.highwire.dtl.DTLVardef@590b29_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1.C_FLOATNO Schematic representation of trogocytosis-mediated acquisition of NLC-derived FOLR2 by CLL cells, and its impact on promoting cancer cell adaptability to folate deprivation. 1) CLL cells enter the lymph node (LN) and engage in contact with FOLR2+ NLCs. 2) The presence of T cell- and stromal cell-derived cytokines, CD40L and IL-15 promotes the activation and trogocytosis-mediated acquisition of FOLR2 by CLL cells. 3) FOLR2 trogocytic CLL cells have an advantage in folate acquisition and show increased proliferation compared to the remaining population of cancer cells C_FIG SUMMARYO_LICLL cells acquire functional FOLR2 from NLCs via trogocytosis, a process that is closely linked with enhanced CLL cell activation and proliferation in vitro C_LIO_LIIncreased Frequency of FOLR2 expressing macrophages in more aggressive and proliferative cases of CLL. C_LIO_LIFOLR2 is a marker of M2-like protective NLCs in vitro C_LI

cancer biology↗

bioRxiv2021

An Agent-Based Model of monocyte differentiation into Tumour-Associated Macrophages in Chronic Lymphocytic Leukemia

Monocyte-derived macrophages help maintain tissue homeostasis and defend the organism against pathogens. In tumors, recent studies have uncovered complex macrophage populations, including tumor-associated macrophages, which support tumorigenesis through cancer hallmarks such as immunosuppression, angiogenesis or matrix remodeling. In the case of chronic lymphocytic leukemia, these macrophages are known as nurse-like cells and they protect leukemic cells from spontaneous apoptosis contributing to their chemoresistance. We propose an agent-based model of monocyte differentiation into nurse-like cells upon contact with leukemic B cells in vitro. We performed patient-specific model calibrations using cultures of peripheral blood mononuclear cells from patients. Using our model, we were able to reproduce temporal survival dynamics of cancer cells in a patient-specific manner and to identify patient groups related to distinct macrophage phenotypes. Our results show a potentially important role of phagocytosis in the polarization process of nurse-like cells and in promoting cancer cells enhanced survival.

systems biology↗

bioRxiv2020

A Boolean Model of the Formation of Tumour Associated Macrophages in an in-vitro Model of Chronic Lymphocytic Leukaemia

The tumour microenvironment is the collection of cells in and surrounding cancer cells in a tumour including a variety of immune cells, especially neutrophils and monocyte-derived macrophages. In a tumour setting, macrophages encompass a spectrum between a tumour-suppressive (M1) or tumour-promoting (M2) state. The biology of macrophages found in tumours (Tumour Associated Macrophages) remains unclear, but understanding their impact on tumour progression is highly important. In this paper, we perform a comprehensive analysis of a macrophage polarization network, following two lines of enquiry: (i) we reconstruct the macrophage polarization network based on literature, extending it to include important stimuli in a tumour setting, and (ii) we build a dynamical model able to reproduce macrophage polarization in the presence of different stimuli, including the contact with cancer cells. Our simulations recapitulate the documented macrophage phenotypes and their dependencies on specific receptors and transcription factors, while also elucidating the formation of a special type of tumour associated macrophages in an in-vitro model of chronic lymphocytic leukaemia. This model constitutes the first step towards elucidating the cross-talk between immune and cancer cells inside tumours, with the ultimate goal of identifying new therapeutic targets that could control the formation of tumour associated macrophages in patients.

systems biology↗