Moffitt, M. | bioRxiv Science

bioRxiv2026

Hoxb5+ fetal liver hematopoietic stem cells establish lifelong hematopoiesis and exhibit enhanced ITGA4-dependent engraftment

Adult long-term hematopoietic stem cells (LT-HSCs) are classically defined by self-renewal, multilineage regenerative capacity, and relative quiescence, but how and when lifelong LT-HSCs are established during development remains unclear. Here, we demonstrate that Hoxb5 fetal liver HSCs exhibit bona fide LT-HSC activity, including long-term multilineage reconstitution and serial transplantation capacity, whereas Hoxb5- fetal liver HSCs display limited regenerative potential. Embryonic lineage tracing further demonstrates that E14.5 Hoxb5-expressing hematopoietic cells contribute broadly to adult hematopoiesis, including the adult HSC compartment, and give rise to functional adult LT-HSCs. Across developmental stages, single-cell transcriptional profiling revealed that fetal Hoxb5 HSCs remain highly proliferative while maintaining canonical LT-HSC transcriptional programs and superior repopulating activity relative to predominantly quiescent adult Hoxb5 HSCs. Fetal Hoxb5 HSCs also exhibited elevated ITGA4-mediated adhesion programs, and disruption of the ITGA4-VCAM1 axis impaired engraftment following transplantation. Together, these findings establish a developmental continuum linking fetal and adult LT-HSCs and identify enhanced ITGA4-mediated adhesion as a defining feature of fetal LT-HSCs.

developmental biology↗

bioRxiv2024

A Method for Electrical Stimulus Artifact Removal Exploiting Neural Refractoriness: Validation by Contrasting Cathodic and Anodic Stimulation

ObjectiveTo present a novel method for removing stimulus transient that exploits the absolute refractory period of electrically excitable neural tissues. BackgroundElectrical stimulation often generates significant signal artifacts that can obscure important physiological signals. Removal of the artifact and understanding latent information from these signals could provide objective measures of circuit engagement, potentially driving advancements in neuromodulation research and therapies. MethodsWe conducted intracranial physiology studies on five consecutive patients with Parkinsons disease who underwent deep brain stimulation (DBS) surgery as part of their routine care. Monopolar stimuli (either cathodic or anodic) were delivered in pairs through the DBS electrode across a range of inter-stimulus intervals. Recordings from adjacent unused electrode contacts used broadband sampling and precise synchronization to generate a robust template for the stimulus transient during the absolute refractory period. These templates of stimulus transient were then subtracted from recordings at different intervals to extract and analyze the residual neural potentials. ResultsAfter artifact removal, the residual signals exhibited absolute and relative refractory periods with timing indicative of neural activity. Cathodic and anodic DBS pulses generated distinct patterns of local tissue activation, showing phase independence from the prior stimulus. The earliest detectable neural responses occurred at short peak latencies (ranging from 0.19 to 0.38 ms post-stimulus) and were completely or partially obscured by the stimulus artifact prior to removal. Cathodic stimuli produced stronger local tissue responses than anodic stimuli, aligning with clinical observations of lower activation thresholds for cathodic stimulation. However, cathodic and anodic pulses induced artifact patterns that were equivalent but opposite. InterpretationThe proposed artifact removal technique enhances prior approaches by allowing direct measurement of local tissue responses without requirements for stimulus polarity reversal, template scaling, or specialized filters. This approach could be integrated into future neuromodulation systems to visualize stimulus-evoked neural potentials that would otherwise be obscured by stimulus artifacts.

bioengineering↗