Biology subjects

Brückner, D.

Publications and source records attributed to Brückner, D..

2 recordsLinked to original sources

bioRxiv2026

Interpretable decoding of cell fate from a snapshot of combinatorial signaling

How combinatorial cell signaling controls cellular decisions in the face of crosstalk is a fundamental problem in biology. A key open question is whether a single snapshot of signaling is sufficient to predict cell fate, especially given substantial evidence that signaling dynamics shape fate decisions. Here, we show that a snapshot of combinatorial signaling accurately predicts cell fate at the single-cell level in a model for human embryonic patterning. To this end, we developed Sig2Fate, a quantitative method integrating iterative immunofluorescence, information theory, and machine learning. Cell fate is encoded by combinatorial yet redundant signaling that reduces to a single angular coordinate in the high-dimensional signaling space, providing a simple interpretation of the signal-to-fate map. This map generalizes across variations in BMP concentration and pharmacological perturbations of ERK, Wnt, and YAP signaling, enabling prediction of drug responses from control data alone when signaling crosstalk is accounted for. Our findings provide a framework for predicting and explaining complex phenotypes from signaling perturbations across biological systems.

developmental biology↗

bioRxiv2026

Single-cell quantification of the iron-neuromelanin balance in dopaminergic neurons across the lifespan

Dopaminergic neurons in the substantia nigra depend on iron for dopamine synthesis but are vulnerable to iron-induced oxidative stress. Many of these neurons synthesize neuromelanin, an iron-chelating pigment that accumulates across the lifespan and makes them vulnerable in Parkinsons disease. It remains unclear whether their selective vulnerability arises from neuromelanin overload or from the release of toxic labile iron from the oversaturated pigment. We quantified iron and neuromelanin at the single-cell level across the lifespan of chimpanzees, a species closely resembling humans in pigment and iron accumulation. Combining quantitative MRI, X-ray fluorescence imaging, and microscopic colorimetry, we found that the iron-to-neuromelanin ratio remains stable with age across large neuronal populations. Chemical equilibrium modeling of the iron binding in neuromelanin indicated that cytosolic labile iron concentrations remain low throughout adulthood. We have found no evidence for neuromelanin saturation or increased iron-mediated toxicity with age. This finding challenges the hypothesis that neuromelanin saturation drives age-related dopaminergic vulnerability. The presented method provides a quantitative framework for studying iron homeostasis in these neurons.

neuroscience↗