Biology subjects

Bjorklund, A. K.

Publications and source records attributed to Bjorklund, A. K..

4 recordsLinked to original sources

bioRxiv2023

Postnatal FGF-signalling establishes gradients of cell-identities along the proximal-distal axis of the lung airways

Secretory cells are major structural and functional constituents of the lung airways. Their spatial organization and specification mechanisms are partially understood. Here, we labelled major secretory airway cell types and analysed them at single-cell resolution. We found opposing, partially overlapping gene-expression gradients along the proximal-distal airway axis superimposed on a general gene program encoding detoxification. One graded program is elevated proximally and relates to innate immunity, whereas the other is enriched distally, encoding lipid metabolism and antigen presentation. Intermediately positioned cells express low levels of both graded programs and show increased clonogenic potency in vitro, relating cell-plasticity to location in each branch. Single-cell RNA-sequencing following lineage-tracing revealed the sequential and postnatal establishment of the gradients in common epithelial progenitors. Fgfr2b is distally enriched and its postnatal inactivation reduces distal gene expression and expands proximal genes into distally located cells. This suggests a central role of FGFR-signaling in tissue-scale airway patterning.

cell biology↗

bioRxiv2021

Reprogrammed iBlastoids contain amnion-like cells but not trophectoderm

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of embryo models hinges on their molecular, cellular and structural fidelities to their in vivo counterparts. To authenticate human embryo models, single-cell RNA-sequencing has been utilised for unbiased transcriptional profiling. However, a well-organised and integrated human single-cell RNA-sequencing dataset, serving as a universal reference for benchmarking human embryo models, remains unavailable. Herein, we developed such a reference, through integration of six published human datasets covering developmental stages from the zygote to the gastrula. Lineage annotations are contrasted and validated with available human and non-human primate datasets. Using stabilised UMAP we constructed a web tool, where query datasets can be projected on the reference and annotated with predicted cell identities. Using this reference tool, we examined several recent human embryo models, highlighting the risk of misannotation when relevant references are lacking.

developmental biology↗

bioRxiv2020

Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts

Transcriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we performed a comprehensive analysis of cytosolic and nuclear transcriptomes in human fetal and adult brain samples. We show significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. Transcripts displaying differential subcellular localization belong to particular functional categories and display tissue-specific localization patterns. We also show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Further investigation of the use of the cytosolic or the nuclear transcriptome for differential gene expression analysis indicates important differences in results depending on the cellular compartment. These differences were manifested at the level of transcript types and the number of differentially expressed genes. Our data provide a resource of RNA subcellular localization in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for differential expression analysis.

molecular biology↗

bioRxiv2019

Single Cell Gene Expression Analysis Reveals Human Stem Cell-Derived Graft Composition in a Cell Therapy Model of Parkinson’s Disease

Since the pioneering studies using fetal cell transplants in Parkinsons disease (PD), brain repair by cell replacement has remained a long-standing and realistic goal for the treatment of neurodegenerative disorders including PD. Authentic and functional midbrain dopamine (DA) neurons can now be generated from human pluripotent stem cells (hPSCs) via a floor plate intermediate1,2, and these cell preparations are both safe and functional when transplanted to animal models of PD3. However, although resulting grafts from fetal brain tissue and hPSCs contain large numbers of desired DA neurons, these therapeutic cells are a minor component of the grafts. Moreover, the cellular composition of the graft has remained difficult to assess due to limitations in histological methods that rely on pre-conceived notions concerning cell types. Here, we used single cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from ventral midbrain (VM)-patterned human embryonic stem cells (hESCs) and VM fetal tissue after long-term survival and functional maturation in a pre-clinical rat model of PD. The analyses revealed that while both cell preparations gave rise to neurons and astrocytes, oligodendrocytes were only detected in grafts of fetal tissue. On the other hand, a cell type closely resembling a class of newly identified perivascular-like cells was identified as a unique component of hESC-derived grafts. The presence of these cells was confirmed in transplants from three different hESC lines, as well as from iPSCs. Thus, these experiments have addressed one of the major outstanding questions in the field of cell replacement in neurological disease by revealing graft composition and differences between hESC- and fetal cell-derived grafts, which can have important implications for clinical trials.

neuroscience↗