Biology subjects

Nolling Jensen, K.

Publications and source records attributed to Nolling Jensen, K..

3 recordsLinked to original sources

bioRxiv2025

Neonatal Microglia and Their Secretome as Mediators of Brain Repair

Microglia are essential regulators of myelin integrity and repair, yet their regenerative capacity declines with ageing and in neurodegenerative diseases such as multiple sclerosis (MS). Neonatal microglia retain a uniquely reparative program that may offer insight into restoring lost functions in the adult CNS. Here we show that transplantation of neonatal microglia ameliorates disability, reduces leukocyte infiltration, and promotes remyelination in both inflammatory (EAE) and non-inflammatory (cuprizone) models, and reverses cognitive decline in aged mice. These benefits persisted even when transplanted cells remained confined to the meninges and were reproduced by the neonatal microglia secretome, indicating a paracrine mechanism. Multi-omic profiling revealed that the neonatal secretome is enriched in trophic factors and membrane-building lipids compared to adult microglia, while transcriptomic analyses of treated aged brains showed reactivation of developmental repair pathways and suppression of inflammatory signatures. Together, these results demonstrate that neonatal microglia re-engage rejuvenation-like programs in the adult CNS and highlight the importance of multifactorial strategies, integrating trophic, metabolic, and immunomodulatory cues, over single-target approaches. Our findings establish early microglial programs as a paradigm for designing new regenerative therapies for CNS disorders.

neuroscience↗

bioRxiv2024

Single-cell analysis of human airway epithelium identifies cell type-specific responses to Aspergillus and Coccidioides

Respiratory fungal infections pose a significant threat to human health. Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment in vitro and investigate cellular responses to two diverse, clinically significant fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii. To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with A. fumigatus and C. posadasii triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either A. fumigatus or C. posadasii, providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways. ImportanceFungal infections in the lungs are dreaded complications for those with compromised immune systems and have limited treatment strategies available. These options are restricted further by the increased prevalence of treatment-resistant fungi. Many studies focus on how our immune systems respond to these pathogens, yet airway epithelial cells remain an understudied component of fungal infections in the lungs. Here, the authors provide a transcriptional analysis of primary human airway epithelial cells stimulated by two distinct fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii. These data will enable further mechanistic studies of the contribution of the airway epithelium to initial host responses and represent a powerful new resource for investigators.

immunology↗

bioRxiv2019

The BLIMP1 - EZH2 nexus in a non-Hodgkin lymphoma

Waldenstroms macroglobulinemia (WM) is a non-Hodgkin lymphoma, resulting in antibody-secreting lymphoplasmacytic cells in the bone marrow and pathologies resulting from high levels of monoclonal immunoglobulin M (IgM) in the blood. Despite the key role for BLIMP1 in plasma cell maturation and antibody secretion, its potential role in WM cell biology has not yet been explored. Here we provide evidence of a crucial role for BLIMP1 in the survival of WM cells and further demonstrate that BLIMP1 is necessary for the expression of the histone methyltransferase EZH2 in both WM and multiple myeloma. The effect of BLIMP1 on EZH2 levels is post translational, at least partially through the regulation of proteasomal targeting of EZH2. Chromatin immunoprecipitation analysis and transcriptome profiling suggest that the two factors co-operate in regulating genes involved in cancer cell immune evasion. Co-cultures of natural killer cells and WM cells further reveal that both factors participate directly in immune evasion, promoting escape from natural killer cell mediated cytotoxicity. Together, the interplay of BLIMP1 and EZH2 plays a vital role in promoting the survival of WM cells.

cancer biology↗