Biology subjects

Tur, S.

Publications and source records attributed to Tur, S..

3 recordsLinked to original sources

bioRxiv2026

Snurportin-1 maintains muscle niche integrity and myogenic progenitor homeostasis

Loss-of-function variants in SNUPN, encoding the nuclear import factor Snurportin-1 (SPN1) required for spliceosomal small nuclear ribonucleoprotein (snRNP) transport, cause a recently described form of limb-girdle muscular dystrophy (LGMD). However, the role of SPN1 in skeletal muscle homeostasis remains poorly understood, in part due to the lack of a suitable in vivo model. Here, we generated a zebrafish snupn loss-of-function model that recapitulates key features of the skeletal muscle phenotype observed in patients. Mutant larvae developed severe locomotor impairment by 6 days post-fertilization (dpf), accompanied by sarcomeric disorganization and impaired muscle fiber integrity. Transcriptomic profiling at 6 dpf revealed widespread alternative splicing and transcriptional dysregulation, with prominent alterations in extracellular matrix and basement membrane components, together with upregulation of stress- and inflammation-associated genes. Notably, these late-stage abnormalities were preceded by disruption of the muscle progenitor population at 2 dpf, with reduced Pax7 progenitor abundance and myogenic gene expression together with altered muscle differentiation and organization. Together, these findings identify SPN1 as a key regulator of skeletal muscle homeostasis linking RNA processing to extracellular niche integrity and myogenic progenitor maintenance. This zebrafish model provides an in vivo platform for dissecting LGMD-associated disease mechanisms and developing therapeutic strategies aimed at restoring muscle function and regenerative capacity.

genetics↗

bioRxiv2025

Trimodal Single-Cell Gene Regulatory Networks Reveal Principles of Stemness Loss and Cell Fate Acquisition in Human Hematopoiesis

Hematopoiesis requires the coordinated loss of stemness and acquisition of lineage identity, yet the regulatory logic and principles underlying these transitions has remained elusive. Single-cell studies suggest that hematopoietic stem and progenitor cells progress along continuous trajectories, but this view conflicts with the existence of discrete, functionally validated populations. Here, we establish the first dynamic, enhancer-based gene regulatory networks (eGRNs) that resolve the molecular programs underlying early human hematopoietic fate decisions. Built on a high-resolution trimodal framework generated with TEA-seq, these networks integrate simultaneously measured transcription factor abundance, enhancer and promoter accessibility, and gene expression within single-cell trajectories anchored to immunophenotypically defined populations. Our framework reveals that stemness loss and lineage acquisition are temporally and mechanistically uncoupled: stemness programs decline gradually through reduced TF abundance long before chromatin closure, whereas lineage identity emerges stepwise through enhancer reconfiguration and activation of lineage-defining eGRNs. This process generates discrete regulatory states that align with immunophenotypically defined populations. Together, these findings reconcile continuous and discrete models of hematopoiesis and establish eGRNs as a powerful framework for defining cell types by their regulatory logic. In addition, we provide an interactive web-based resource to facilitate further investigation of eGRNs and trajectories during early human hematopoiesis.

genomics↗

bioRxiv2024

Caspase-Activated DNase Localizes to Cancer Causing Translocation Breakpoints During Cell Differentiation

Caspase activated DNase (CAD) induced DNA breaks promote cell differentiation and therapy-induced cancer cell resistance. CAD targeting activity is assumed to be unique to each condition, as differentiation and cancer genesis are divergent cell fates. Here, we made the surprising discovery that a subset of CAD-bound targets in differentiating muscle cells are the same genes involved in the genesis of cancer-causing translocations. In muscle cells, a prominent CAD-bound gene pair is Pax7 and Foxo1a, the mismatched reciprocal loci that give rise to alveolar rhabdomyosarcoma. We show that CAD-targeted breaks in the Pax7 gene are physiologic to reduce Pax7 expression, a prerequisite for muscle cell differentiation. A cohort of these CAD gene targets are also conserved in early differentiating T cells and include genes that spur leukemia/lymphoma translocations. Our results suggest the CAD targeting of translocation prone oncogenic genes is non-pathologic biology and aligns with initiation of cell fate transitions.

genomics↗