Biology subjects

Kol, A.

Publications and source records attributed to Kol, A..

3 recordsLinked to original sources

bioRxiv2019

Salmonella Enhances Osteogenic Differentiation in Adipose-Derived Mesenchymal Stem Cells

The potential of mesenchymal stem cells (MSCs) for tissue repair and regeneration has garnered great attention. While MSC interaction with microbes at sites of tissue damage and inflammation is likely, especially in the gut, the consequences of bacterial association have yet to be elucidated. This study investigated the effect of Salmonella enterica ssp enterica serotype Typhimurium on MSC trilineage differentiation path and mechanism. Through examination of key markers of differentiation, immunomodulatory regulators, and inflammatory cytokines, we demonstrated that Salmonella altered osteogenic and chondrogenic differentiation pathways in human and goat adipose-derived MSCs. Gene expression profiles defined signaling pathway alterations in response to Salmonella association not observed in epithelial cells. We uncovered significant differential expression (P < 0.05) of genes associated with anti-apoptotic and pro-proliferative responses in MSCs during Salmonella challenge. These observations led us to conclude that bacteria, specifically Salmonella, induce pathways that influence functional differentiation trajectories in MSCs, thus implicating substantial microbial influence on MSC physiology and immune activity.

microbiology↗

bioRxiv2019

Astrocytes Contribute to Remote Memory Formation by Modulating Hippocampal-Cortical Communication During Learning

The consolidation and retrieval of remote memories depend on the coordinated activity of the hippocampus and frontal cortices. However, the exact time at which these regions are recruited to support memory and the interactions between them are still debated. Astrocytes can sense and modify neuronal activity with great precision, but their role in cognitive function has not been extensively explored. To investigate the role of astrocytes in remote memory we expressed the Gi-coupled receptor hM4Di in CA1 astrocytes, allowing their manipulation by a designer drug. We discovered that astrocytic modulation during learning resulted in a specific impairment in remote, but not recent, memory recall, accompanied by decreased neuronal activity in the anterior cingulate cortex (ACC) during retrieval. We revealed a massive recruitment of ACC-projecting neurons in CA1 during memory acquisition, accompanied by activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in-vivo, and reduced the downstream response in the ACC. This same manipulation in behaving mice induced a projection-specific inhibition of ACC-projecting CA1 neurons during learning, consequently preventing the recruitment of the ACC. Our findings suggest that the foundation of remote memory is established in the ACC during acquisition, engaging a distinct process from the one supporting consolidation of recent memory. Furthermore, the mechanism underlying remote memory involves projection-specific functions of astrocytes in regulating neuronal activity.

neuroscience↗

bioRxiv2018

TGF-β induced CXCL13 in CD8+ T cells is associated with tertiary lymphoid structures in cancer

Coordinated immune responses against human tumors are frequently characterized by tertiary lymphoid structures (TLS) which predict improved prognosis. The development of TLS is dependent on the chemokine CXCL13, reported to be secreted by dendritic cells and follicular helper T cells only. We report the unexpected finding that CXCL13 is also secreted by activated CD8+ T cells following stimulation by transforming growth factor beta (TGF-{beta}). Using single cell RNA sequencing we found that expression of CXCL13 in CD8+ T cells was restricted to the intraepithelial CD103+ population. Accordingly, CD8+ T cells activated in the presence of TGF-{beta} simultaneously upregulated CD103 and secreted CXCL13. CXCL13 expression was strongly correlated with neo-antigen burden and cytolytic gene signatures in bulk tumors. In line with this, TLS were abundant in neo-antigen-high, CD103+ T cell-enriched tumors. TGF-{beta} thus appears to play a role in coordinating immune responses against human tumors through CD8-dependent CXCL13-associated formation of TLS.

immunology↗