Biology subjects

Zogu, B.

Publications and source records attributed to Zogu, B..

3 recordsLinked to original sources

bioRxiv2026

Generation of human iPSC-derived motor neurons with defined regional identities across the rostrocaudal axis

This study establishes a unified pipeline for generating human induced pluripotent stem cell (iPSC)-derived motor neurons (iMNs) with defined hindbrain, cervical, and lumbar identities to support anatomically resolved studies of motor neuron development and degeneration. Conventional differentiation methods can efficiently produce iMNs but provide limited control over rostrocaudal identity and frequently generate populations with heterogeneous HOX profiles. We addressed this limitation by optimizing developmental morphogen combinations and treatment windows, establishing three complementary protocols that reproducibly generated hindbrain/rhombomere-associated motor neurons (RiMNs), cervical motor neurons (CiMNs), and lumbar motor neurons (LiMNs) across iPSC lines from six non-diseased donors balanced by sex. Transcriptomic and protein analyses demonstrated graded rostrocaudal specification from RiMNs through CiMNs to LiMNs, together with region-appropriate motor neuron subtype features. These identities showed the expected relationships to human week 9 fetal rostrocaudal HOX programs. High-density multielectrode array analysis further revealed synchronized network firing, electrically active neurite networks, and enhanced axonal signal propagation in the regional iMN populations compared with conventionally differentiated iMNs. Spike-sorted recordings additionally revealed protocol-associated differences in single-neuron electrophysiological profiles. Together, this three-protocol pipeline enables the reproducible generation and comparative analysis of anatomically defined human motor neuron populations and provides region-matched cellular models for investigating motor neuron development, selective degeneration, and therapeutic responses.

neuroscience↗

bioRxiv2026

A region-delineated snRNA-seq atlas of mouse spinal cord across lifespan resolves the interaction of normative aging programs with SOD1-G93A ALS

Aging is the strongest risk factor for amyotrophic lateral sclerosis (ALS), yet how normative aging programs intersect with disease mechanisms remain unclear. Here we generated a lifespan-resolved, cell type-and region-specific single-nucleus RNA-sequencing atlas of the mouse spinal cord spanning embryonic development through advanced age in WT mice and end-stage disease in the SOD1-G93A ALS model. This resource enabled systematic comparison of physiological aging trajectories with disease-associated transcriptional changes across spinal cord cell types and rostrocaudal regions. We found that SOD1-G93A transcript and protein states differed markedly across spinal regions during disease onset and progression, and these molecular patterns paralleled the relative resilience of cervical regions and the heightened vulnerability of lumbar regions to degeneration in this transgenic mouse model. Prior to disease onset, we identified reduced ubiquitin expression that primed region-specific disruption of proteostasis in the SOD1-G93A spinal cord. Despite these disease-associated changes, aging-related transcriptional programs were largely preserved across most cell types, arguing against a global acceleration of aging in ALS. Instead, microglia emerged as a key exception, exhibiting accelerated and rewired aging- and disease-associated gene expression modules regulated by MITF and NRF2. Together, these findings provide an anatomically, cellularly, and temporally resolved framework for understanding how aging programs interact with disease-specific pathways to shape regional dysfunction and neurodegeneration in ALS.

neuroscience↗

bioRxiv2020

Developing methods for measuring national distributions and densities of wild mammals using camera traps: A Kosovo study

Understanding the distributions and density of wild mammals is integral to the implementation of wildlife management strategies, particularly for controlling diseases and conservation management. Recent advances in camera trap technology together with the development of the Random Encounter Model have provided a non-invasive method for estimating mammal densities. In addition, the development of citizen science initiatives have advanced ecological data collection. This study describes a national camera trap survey delivered by local stakeholders in eleven forest sites in Kosovo from 2014 to 2015 to measure the distributions and abundance of medium to large wild mammals as part of the Control and/or eradication of animal diseases project. The Random Encounter Model was used to calculate density data for each species, which appear realistic when compared to densities found in other European countries. The study particularly focussed on the red fox (Vulpes vulpes) and the grey wolf (Canis lupus) as potential vectors of rabies and wild boar (Sus scrofa) as a vector of classical swine fever. These species were found to be three of the most widely distributed species in Kosovo and were present at the majority of sites at high densities. The camera survey also provided information on species of conservation concern such as the Eurasian brown bear (Ursus arctos) and provided the first physical evidence of a live Eurasian golden jackal (Canis aureus) in Kosovo. Although sources of bias were identified, these estimates are likely to be more accurate than those devised from methods such as hunting bags and the findings of this study suggest that, with a moderate amount of development, camera trapping implemented by local stakeholders can be used as an effective and practicable method to estimate national distributions and population sizes of medium to large sized wild mammals.

ecology↗