Biology subjects

Boehme, L.

Publications and source records attributed to Boehme, L..

5 recordsLinked to original sources

bioRxiv2023

A spatial human thymus cell atlas mapped to a continuous tissue axis

T cells develop from circulating precursors, which enter the thymus and migrate throughout specialised sub-compartments to support maturation and selection. This process starts already in early fetal development and is highly active until the involution of the thymus in adolescence. To map the micro-anatomical underpinnings of this process in pre- vs. post-natal states, we undertook a spatially resolved analysis and established a new quantitative morphological framework for the thymus, the Cortico-Medullary Axis. Using this axis in conjunction with the curation of a multimodal single-cell, spatial transcriptomics and high-resolution multiplex imaging atlas, we show that canonical thymocyte trajectories and thymic epithelial cells are highly organised and fully established by post-conception week 12, pinpoint TEC progenitor states, find that TEC subsets and peripheral tissue genes are associated with Hassalls Corpuscles and uncover divergence in the pace and drivers of medullary entry between CD4 vs. CD8 T cell lineages. These findings are complemented with a holistic toolkit for spatial analysis and annotation, providing a basis for a detailed understanding of T lymphocyte development.

immunology↗

bioRxiv2022

Weddell seals near the fastest melting glacier in Antarctica prefer shallow, coastal and partially ice-covered waters

Antarctic ice-shelves melting is accelerating, and the highest rates for the continent are observed in the Amundsen Sea, where Weddell seals are understudied. By modelling an unrivalled telemetry tracking dataset, we show that this top predator in the area is more likely found in shallower waters, closer to the coast, half-covered by ice and where the temperature at the ocean bottom is around 0.5{degrees}C or colder. Their distribution during winter is more restricted to coastal areas in the eastern Amundsen Sea and spread out in warmer months. That fluctuation reflects the drastic variation in their habitat illustrating their potential sensitivity to the upcoming impacts of climate changes. We discuss their overlap with Antarctic toothfish fisheries in the area and the potential consequences of global warming to the ecology of the seals.

ecology↗

bioRxiv2020

Sex-specific variation in the use of vertical habitat by a resident Antarctic top predator

Patterns of habitat use are commonly studied in horizontal space, but this does not capture the four-dimensional nature of ocean habitats. There is strong seasonal variation in vertical ocean structuring, particularly at the poles, and deep-diving marine animals encounter a range of oceanographic conditions. We use hidden Markov models fitted to telemetry data from an air-breathing top predator to identify different diving behaviours and understand usage patterns of vertically distributed habitat. We show that preference for oceanographic conditions in the Weddell Sea, Antarctica, varies by sex in Weddell seals, and present the first evidence that both sexes use high-density, continental shelf water masses. Males spend more time in the colder, unique high-salinity shelf water masses found at depth, while females also venture off the continental shelf and visit warmer, shallower pelagic water masses. Both sexes exhibit a diurnal pattern in diving behaviour that persists from austral autumn into winter. These findings provide insights into the Weddell Sea shelf and open ocean ecosystem from a top predator perspective. The differences in habitat use in a resident, sexually monomorphic Antarctic top predator suggest a different set of needs and constraints operating at the intraspecific level, which are not driven by body size.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2019

Intellectual disability-associated factor Zbtb11 cooperates with NRF-2/GABP to control mitochondrial function

Zbtb11 is a conserved transcription factor mutated in families with hereditary intellectual disability. Its precise molecular and cellular functions are currently unknown, precluding our understanding of the aetiology of this disease. Using a combination of functional genomics, genetic and biochemical approaches here we show that Zbtb11 plays essential roles in maintaining the homeostasis of mitochondrial function. Mechanistically, we find Zbtb11 facilitates the recruitment of Nuclear Respiratory Factor 2 (NRF-2) to its target promoters, activating a subset of nuclear genes with roles in the biogenesis of respiratory complex I and the mitoribosome. Genetic inactivation of Zbtb11 resulted in a severe complex I assembly defect, impaired mitochondrial respiration, mitochondrial depolarisation, and ultimately proliferation arrest and cell death. Experimental modelling of the pathogenic human mutations showed these have a destabilising effect on the protein, resulting in reduced Zbtb11 dosage, down-regulation of its target genes, and impaired complex I biogenesis. Our study establishes Zbtb11 as a novel essential mitochondrial regulator, improves our understanding of the transcriptional mechanisms of nuclear control over mitochondria, and provides a rationale for the aetiology of Zbtb11-associated intellectual disability.

cell biology↗

bioRxiv2019

Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

evolutionary biology↗