Biology subjects

Broberg, M.

Publications and source records attributed to Broberg, M..

3 recordsLinked to original sources

bioRxiv2026

Homothallic or heterothallic? A genomic investigation into the sexual capabilities of the ascomycete fungus Clonostachys rosea

Modes of reproduction and sexual strategies strongly influence the genetic diversity and evolutionary potential of a species. The ascomycete fungus Clonostachys rosea is reported to be homothallic (sexually self-fertile), although a rapid decay of genome-wide linkage disequilibrium is also reported, something that is not in line with an obligate homothallic mode of reproduction. To investigate this phenomenon, we identified the mating-type (MAT1) locus in 66 genome-sequenced C. rosea strains under the hypothesis that each strain contains genes from both MAT1 idiomorphs. Eleven strains indeed contained both MAT1-1 and MAT1-2 genes, suggesting homothallism. However, most strains harboured either MAT1-1 or MAT1-2 genes and co-existed in North America, Europe and China, suggesting heterothallism. The MAT1 locus of heterothallic strains was highly conserved, and the linkage disequilibrium half decay distance was 1050 bp, suggesting sexual outcrossing. The presence of conserved MAT1-1 or MAT1-2 idiomorphs in strains of other Clonostachys species shows that heterothallism is likely the ancestral state. A phylogenetic analysis of 2800 single-copy orthologous genes revealed that homothallic and heterothallic strains separated in two well-supported clades, indicating a single lineage of homothallic C. rosea, likely originating in South America, followed by intercontinental dispersal. Homothallic C. rosea strains displayed higher nucleotide diversity than heterothallic strains, indicating a lack of outcrossing. This unique case of both homothallic and heterothallic lineages within the same species provides an opportunity to study the genomic consequences of selfing in very closely related strains.

evolutionary biology↗

bioRxiv2025

Alanine catabolism of Paneth cells maintains intestinal stem cell function during dietary restriction

Background and aimsPaneth cell niche promotes the function of intestinal stem cells (ISCs) during reduced food intake, but how ISC activity can be boosted when availability of resources is simultaneously reduced remains unknown. MethodsMice were subjected to dietary restriction (DR) and ad libitum (AL) dietary regime. FACS-sorted DR and AL Paneth cells and Lgr5+ stem cells were co-cultured, and organoid formation supportive capacity of Paneth cells was assessed. The role of Gpt2 - a Paneth cell specific mitochondrial alanine transaminase, was investigated by targeting pharmacologically and genetically in the intestinal organoids. By using U-13C labelled Alanine, an intercellular metabolic exchange assay was developed - and a conversion and transport of lactate from Paneth cells to stem cells, was followed by metabolomics. The in vivo role of Gpt2 was investigated in a conditional knock out mouse model. ResultsWe discovered that an increase in ISC function upon dietary restriction (DR) or DR mimicking condition, is dependent on Gpt2 in Paneth cells. Metabolic tracing of alanine directly showed DR boosts Paneth cell alanine catabolism, increasing lactate production via gluconeogenesis. Alanine derived lactate is shuttled from Paneth cells to neighboring stem cells, promoting TCA cycle and enhancing the ISC function during DR. Correspondingly, pharmacologic inhibition in vitro and genetic targeting of Gpt2 in vivo abolished the DR induced capacity of Paneth cells to support ISC function. ConclusionsOur results unravel dynamic intercellular metabolic cooperation in tissue adaptation, where Paneth cells upregulated Gpt2 catabolize increased amount of alanine to generate lactate as a transferable energy source, and to augment stem cell functions under DR.

cell biology↗

bioRxiv2023

SIRPα controls CD47-dependent platelet clearance in mice and humans

Over the last decade, more data has revealed that increased surface expression of the "dont eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRP can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRP signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRP axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRP axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at the SIRPA locus that impact platelet levels in humans such that higher SIRPA gene expression is associated with higher platelet levels. SIRPA expression at either end of the normal range may affect clinical outcomes of treatment with anti-CD47 therapy. Key pointsO_LIPlatelet homeostasis is regulated through the CD47-SIRP axis and therapeutic blockade to disrupt this interaction impacts platelet levels C_LIO_LICommon genetic variants at SIRPA locus associate with platelet levels C_LI

immunology↗