Biology subjects

Saleem, S.

Publications and source records attributed to Saleem, S..

4 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomics for gene discovery identifies Slc13a5 as a modulator of bone mechanoadaptation

Bone is a dynamic tissue that continuously adapts its structure in response to mechanical loading, an essential process for maintaining skeletal health. However, this adaptive capacity declines with aging, contributing to increased fragility and fracture risk. Developing therapeutic strategies that preserve or restore bone mechanoadaptation in patients with increased bone fragility requires identifying key molecular regulators of this process. We applied spatial transcriptomics (GeoMx, NanoString) to characterize gene expression changes induced by mechanical loading in the murine tibia, focusing on periosteal and bone compartments in regions under tension and compression. Spatial data were validated and cross-compared with previously published bulk RNA-seq and laser-capture microdissection datasets, identifying a set of 12 genes consistently regulated by loading across independent platforms and laboratories. As part of a functional analysis, we selected Slc13a5, a citrate transporter implicated in bone mineralization and metabolism. Conditional deletion of Slc13a5 in osteolineage cells using Osteocalcin-Cre significantly increased the loading-induced mineralizing surface in tensile regions compared with Cre- Slc13a5fl/fl littermates. In addition, Slc13a5 cKO mice exhibited lower resorption around the neutral axis after loading compared to controls. Together, these findings identify Slc13a5 as a regulator of bone adaptation in regions experiencing low mechanical stimulation and suggest it as a potential therapeutic target for conditions characterized by impaired mechanoadaptive responses. This study highlights spatial transcriptomics as a powerful gene discovery framework for bone, enabling identification of novel targets to understand mechanisms and develop therapies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/711126v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@14fc0e9org.highwire.dtl.DTLVardef@1023a16org.highwire.dtl.DTLVardef@133aa0eorg.highwire.dtl.DTLVardef@e19c86_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Xeno-free human iPSC-derived prostate organoid platform for multilineage differentiation and genetic manipulation

Current prostate organoid models rely on tissue-derived material or animal components and lack epithelial and stromal complexity. We defined a xeno-free system to generate human prostate organoids from induced pluripotent stem cells with consistent multilineage differentiation. Floating organoids self-organize into epithelial and stromal domains with basal, luminal, neuroendocrine, fibroblast, and smooth muscle markers. In an alternative modular co-culture system, engineered epithelial progenitors are aggregated with wild-type mesenchymal progenitors, enabling compartment-specific manipulation. Androgen receptor-overexpressing organoids showed increased epithelial AR and PSA expression and proliferation. Single-cell transcriptomics, together with qPCR and immunostaining, confirmed prostate lineage specification and tissue organization. This new xeno-free platform provides a reproducible, scalable, and genetically tractable model to study in-vitro prostate lineage programs, epithelial-stromal interactions, and disease biology. Graphic AbstractThis study describes the generation of prostate organoids from human iPSCs. iPSCs, including those reprogrammed from patients carrying germline mutations, can be differentiated into prostate organoids either through monoculture or by co-culturing endodermal cells with mesenchymal progenitors. Genetic manipulation can be introduced before endoderm specification to model cancer drivers. The resulting multi-lineage organoids exhibit distinct epithelial (AR, NKX3.1, PSA, CK8/18) and stromal (VIM, -SMA) compartments, providing a versatile platform for developmental studies, disease modelling, drug screening, and biomarker discovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/683654v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1cc13eborg.highwire.dtl.DTLVardef@12fe2a4org.highwire.dtl.DTLVardef@c89d64org.highwire.dtl.DTLVardef@d541e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Coagulation factor XII contributes to renin activation, heart failure progression, and mortality

Symptomatic heart failure (sHF) with cardiac dysfunction, edema, and mortality are driven by overactivation of the renin-angiotensin-aldosterone system (RAAS). Renin is widely recognized as a key initiator of RAAS function, yet the mechanisms that activate renin remain a mystery. We discovered that activated coagulation factor XII generates active renin in the circulation and is directly linked to pathological activation of the systemic RAAS, development of sHF, and increased mortality. These findings suggest a new paradigm for therapeutically modulating the RAAS in sHF and other pathological conditions.

pathology↗

bioRxiv2018

Choline Transporter in α/β core neurons of Drosophila mushroom body non-canonically regulates pupal eclosion and maintains neuromuscular junction integrity

Insect mushroom bodies (MB) have an ensemble of synaptic connections well-studied for their role in experience-dependent learning and several higher cognitive functions. MB requires neurotransmission for an efficient flow of information across synapses with the different flexibility to meet the demand of the dynamically changing environment of an insect. Neurotransmitter transporters coordinate appropriate changes for an efficient neurotransmission at the synapse. Till date, there is no transporter reported for any of the previously known neurotransmitters in the intrinsic neurons of MB. In this study, we report a highly enriched expression of Choline Transporter (ChT) in Drosophila MB. We demonstrate that knockdown of ChT in a sub-type of MB neurons called /{beta} core (/{beta}c) neurons leads to eclosion failure, peristaltic defect in larvae, and altered NMJ phenotype. These defects were neither observed on knockdown of proteins of the cholinergic locus in /{beta}c neurons nor by knockdown of ChT in cholinergic neurons. Thus, our study provides insights into non-canonical roles of ChT in MB.

developmental biology↗