Biology subjects

Rawji, K. S.

Publications and source records attributed to Rawji, K. S..

3 recordsLinked to original sources

bioRxiv2025

Spontaneous differentiation across cell lineages of separate germ layer origin during progenitor cell-mediated regeneration of the central nervous system

During CNS regeneration, neuroepithelial-derived oligodendrocyte progenitor cells (OPCs) can cross germ-layer boundaries to generate neural-crest-derived Schwann cells (SCs). However, the underlying mechanism and disease relevance of this unique phenomenon of cellular plasticity is unclear. Here, we combine single cell genomics in rodent models of CNS injury and samples from multiple sclerosis patients to characterise OPC-derived SCs. We discover that integrin signalling and bone morphogenetic protein (BMP) activation activate a core SOX10/OLIG2 transcriptional circuit to drive OPC-to-SC differentiation. We show that OPC-derived SCs myelinate in vitro and in vivo, and unlike peripheral SCs, can integrate into astrocyte-rich territories. Together, these findings define a conserved molecular mechanism of adult plasticity, enabling the control of OPC fate choices beyond their germ layer origin for CNS repair.

neuroscience↗

bioRxiv2025

Dysregulation of transcription networks regulating oligodendrogenesis in age-related decline in CNS remyelination

In demyelinating diseases like multiple sclerosis (MS), efficient remyelination is critical for functional recovery. Remyelination efficiency declines with age, and is linked to progressive disability. The gene regulatory network underlying remyelination, and how it is altered with aging, remains unclear. Here we present a comparative single-nucleus RNA and ATAC sequencing analysis of remyelination in young and aged mice. We identified gene modules dynamically expressed throughout oligodendrocyte differentiation, revealing age-dependent changes in key processes related to myelination. Multi-omic analysis allowed us to map the regulatory network driving efficient remyelination within oligodendrocyte lineage cells in young mice. We highlight key transcription factors in the network dysregulated with age, and we describe similar dysregulations in MS lesions. Modifying the expression of these transcription factors in primary oligodendrocyte progenitor cells impacts differentiation. These findings provide a foundational understanding of this regenerative process in the context of aging and in chronic demyelinating diseases.

neuroscience↗

bioRxiv2023

Circulating Platelets Modulate Oligodendrocyte Progenitor Cell Differentiation During Remyelination

Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (CALRHET), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.

neuroscience↗