Biology subjects

Schaaf, C.

Publications and source records attributed to Schaaf, C..

4 recordsLinked to original sources

bioRxiv2025

Human NKX2.2 influences islet endocrine cell fate choices through regulation of WNT pathway genes

Transcriptional regulation is a key central mechanism of cell fate determination in developing tissues. The homeobox transcription factor NKX2.2 is an essential regulator of mouse and human pancreatic endocrine development, however its precise molecular role in a human system has not been previously investigated. In this study we generated NKX2.2 null (NKX2.2KO) human embryonic stem cell (hESC) lines using CRISPR/Cas9 technologies and differentiated them towards a pancreatic {beta} cell fate using a stem cell-derived {beta} cell differentiation protocol. Functional and transcriptomic analyses of the hESC-derived pancreatic endocrine cells lacking NKX2.2 revealed similarities and differences compared to the molecular functions of NKX2.2 in mice. In the absence of NKX2.2, the {beta} cell differentiations result in reduced numbers of insulin-producing cells, and the differentiations become skewed towards polyhormonal fates, including cells co-expressing insulin, ghrelin and somatostatin. Deletion of NKX2.2 also eliminates the off-target formation of enterochromaffin cells. Single cell transcriptome analysis of the early endocrine cell population revealed a marked disruption of metabolic pathways that was confirmed by comparative metabolite tracing, providing novel insights into the regulation of early endocrine lineage decisions. Furthermore, NKX2.2 directly regulates several genes in the WNT signaling pathway, suggesting this is a key molecular mechanism through which NKX2.2 regulates these islet cell fate decisions in the human system.

developmental biology↗

bioRxiv2024

Oxytocin Gαi signaling-induced amygdala astrocytes processes retraction shapes behavioral stress response

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin- dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology- dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.

neuroscience↗

bioRxiv2023

Lattice-Boltzmann Modelling for Inertial Particle Microfluidics Applications -A Tutorial Review

Inertial particle microfluidics (IPMF) is an emerging technology for the manipulation and separation of microparticles and biological cells. Since the flow physics of IPMF is complex and experimental studies are often time-consuming or costly, computer simulations can offer complementary insights. In this tutorial review, we provide a guide for researchers who are exploring the potential of the lattice-Boltzmann (LB) method for simulating IPMF applications. We first review the existing literature to establish the state of the art of LB-based IPMF modelling. After summarising the physics of IPMF, we then present related methods used in LB models for IPMF and show several case studies of LB simulations for a range of IPMF scenarios. Finally, we conclude with an outlook and several proposed research directions.

biophysics↗

bioRxiv2022

Mid-summer snow-free albedo across the Arctic tundra was mostly stable or increased over the past two decades

Arctic vegetation changes, such as increasing shrub-cover, are expected to accelerate climate warming through increased absorption of incoming radiation and corresponding decrease in summer shortwave albedo. Here we analyze mid-summer shortwave land-surface albedo and its change across the pan-Arctic region based on MODIS satellite observations over the past two decades (2000-2021). In contrast to expectations, we show that terrestrial mid-summer shortwave albedo has not significantly changed in 82% of the pan-Arctic region, while 14% show an increase and 4% a decrease. By analyzing the visible and near-/shortwave-infrared range separately, we demonstrate that the slight increase arises from an albedo increase in the near-/shortwave-infrared range domain while being partly compensated by a decrease in visible albedo. A similar response was found across different tundra vegetation types. We argue that this increase in reflectance is typical with increasing biomass as a result of increased multiple reflection in the canopy. However, CMIP6 global climate model albedo predictions showed the opposite sign and different spatial patterns of snow-free summer albedo change compared to satellite-derived results. We suggest that a more sophisticated vegetation parametrization can reduce this discrepancy, and provide albedo estimates per vegetation type.

ecology↗