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Biology subjects

Steinbeck, F.

Publications and source records attributed to Steinbeck, F..

3 recordsLinked to original sources

An immunophenotype-coupled transcriptomic atlas of mouse hematopoietic progenitors

Decoding the bone marrow (BM) hematopoietic progenitor compartment is central to understanding the development of mature immune cells in health and disease. Single-cell multimodal approaches are transforming the analysis of this heterogeneous compartment by simultaneously capturing transcriptomic and proteomic information. Still, integrated studies covering the full spectrum of murine hematopoietic stem and progenitor cells (HSPCs) remain scarce. Here, we report a Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) based atlas of 9,281 low-frequency mouse BM HSPCs, profiled using a 123 antibody-derived tag (ADT) panel coupled with genome-wide single-cell transcriptomes. Multimodal analysis resolved 28 progenitor stages across eight blood lineages, each defined by distinctive surface marker and transcription factor (TF) profiles, and provided novel marker combinations to dissect transcriptionally closely related progenitor stages. Classical mouse progenitor surface markers, such as CD117, CD34, and CD115, were detected in accordance with well-established lineage relationships, whereas CD43 and CD48 showed, unexpectedly, broader expression patterns. Neglected surface molecules such as CD27, CD36, CD106, and PIR-A/B are nominated as novel stage-specific markers. ADT versus transcriptome comparison revealed transcription-translation inconsistencies for markers, including CD54 and CD68. A CITE-seq-guided gating strategy translates these population definitions into FACS-compatible panels for prospective isolation and functional interrogation of previously unresolved progenitor stages. Comprehensive TF network analysis delineated lineage- and stage-specific transcriptional programs. This contributes to clarifying unresolved ontogenies and functions, including the lympho-myeloid dual origin of pDCs or rapid neutrophil turnover. This new and comprehensive resource enables exploration of mouse hematopoietic progenitor states driving discoveries in hematology and immunology.

immunology↗

Familiarity-taxis: A bilateral approach to view-based navigation.

Many insects use view-based navigation, or snapshot matching, to return to familiar locations, or navigate routes. This relies on egocentric memories being matched to current views of the world. Previous snapshot navigation algorithms have used full panoramic vision for the comparison of memorised images with query images to establish a measure of familiarity, which leads to a recovery of the original heading direction from when the snapshot was taken. Many aspects of insect sensory systems are lateralised with steering being derived from the comparison of left and right signals like a classic Braitenberg vehicle. Here we investigate whether view-based route navigation can be implemented using bilateral visual familiarity comparisons. We found that the difference in familiarity between estimates from left and right fields of view can be used as a steering signal to recover the original heading direction. This finding extends across many different sizes of field of view and visual resolutions. In insects, steering computations are implemented in a brain region called the Lateral Accessory Lobe, within the Central Complex. In a simple simulation we show with a SNN model of the LAL an existence proof of how bilateral visual familiarity could drive a search for a visually defined goal.

animal behavior and cognition↗

Production of adaptive movement patterns via an insect inspired Spiking Neural Network Central Pattern Generator.

Navigation in ever-changing environments requires effective motor behaviours. Many insects have developed adaptive movement patterns which increase their success in achieving navigational goals. A conserved brain area in the insect brain, the Lateral Accessory Lobe, is involved in generating small scale search movements which increase the efficacy of sensory sampling. When the reliability of an essential navigational stimulus is low, searching movements are initiated whereas if the stimulus reliability is high, a targeted steering response is elicited. Thus the network mediates an adaptive switching between motor patterns. We developed Spiking Neural Network models to explore how an insect inspired architecture could generate adaptive movements in relation to changing sensory inputs. The models are able to generate a variety of adaptive movement patterns, the majority of which are of the zig-zagging kind, as seen in a variety of insects. Furthermore, these networks are robust to noise. Because a large spread of network parameters lead to the zig-zagging movement dynamics, we conclude that the investigated network architecture is inherently well suited to generating adaptive movement patterns.

animal behavior and cognition↗