Biology subjects

Lindskog, C.

Publications and source records attributed to Lindskog, C..

22 records · Page 2Linked to original sources

bioRxiv2020

Revealing interspecies transmission barriers of avian influenza A viruses

Influenza A virus (IAV) pandemics result from interspecies transmission events within the avian reservoir and further to mammals including humans. Investigating molecular virus-host interactions dictating this process and the adaptations to the new hosts that follow is vital to understand zoonotic IAV spread. Receptor incompatibility has been suggested to limit zoonotic IAV transmission from the wild bird reservoir. Other barriers to interspecies transmission, particularly within the avian system, largely remain elusive. Through assessment of infection dynamics of mallard origin IAV in two different avian hosts, coupled with studies of receptor expression and host response we aimed to reveal the host-pathogen interactions in a cross-species transmission event. We found that shedding patterns and innate immune responses were highly dependent on viral genotypes, host species and inoculation routes, but less dependent on receptor expression. Further, in contrary to the prevailing dogma we demonstrate that birds can produce a wide range of different sialylated structures also found in mammals, e.g. extended N- and O-linked Neu5Ac2,6 terminated glycans. Overall, receptor incompatibility is not the sole transmission barrier for IAV between birds and to humans, but other host-pathogen factors deserve dedicated studies to achieve proper pandemic preparedness.

microbiology↗

bioRxiv2020

The protein expression profile of ACE2 in human tissues

The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across >150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitutes an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.

cell biology↗

bioRxiv2019

Spatiotemporal dissection of the cell cycle regulated human proteome

Cellular division is a fundamental source of cell-to-cell variability, and studies of transcript and protein abundances have revealed several hundred genes that are regulated by the cell cycle1-8. However, none of these studies provide single-cell resolution of protein expression, leaving an incomplete understanding of cell-to-cell heterogeneity and the roles of cycling transcripts and proteins. Here, we present the first comprehensive map of spatiotemporal heterogeneity of the human proteome by integrating proteomics at subcellular resolution, single-cell transcriptomics, and pseudotime measurements of individual cells within the cell cycle. We identify that 17% of the human proteome displays cell-to-cell variability, of which 26% is correlated to cell cycle progression, and we present the first evidence of cell cycle association for 235 proteins. Only 15% of proteomic cell cycle regulation is due to transcriptomic cycling, which points to other means of regulation such as post-translational modifications. For proteins regulated at the transcript level, we observe a 7.7 hour delay between peak expression of transcript and protein on average. This spatially resolved proteomic map of the cell cycle has been integrated into the Human Protein Atlas and serves as a valuable resource for accelerating molecular studies of the human cell cycle and cell proliferation.

cell biology↗

bioRxiv2018

The human secretome - the proteins secreted from human cells

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving {beta}-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.

molecular biology↗