Biology subjects

Hemati, H.

Publications and source records attributed to Hemati, H..

4 recordsLinked to original sources

bioRxiv2026

Brain Organoids, Lessons from Fetal Neocortex Formation, and Rational Design for Quality Control

Recent widespread adoption of cerebral organoid protocols has led to many new studies assessing the human-specific features of neural diseases. However, not all organoid studies employ proper quality control, which limits the physiological relevance of their findings. Here, we discuss the stages of in vivo neocortex formation and how those stages are recapitulated in organoid protocols. We then present the first guide for real-time operator removal of maldeveloped organoids in shaking culture. Finally, we show preliminary work on an organoid imaging and mesofluidic control platform for automated quality control of organoid development. Taken together, this approach for assessing the morphological features of organoids will improve the rigor and reproducibility of organoid studies, increase effect sizes of physiologically relevant disease etiology, and pave the way for cortical organoid GMP in high-throughput. Clinical RelevanceThis establishes high-throughput, visual brain organoid quality control for disease studies and preclinical testing.

neuroscience↗

bioRxiv2026

Maternal Obesity Reprograms Differentiation Trajectories of Fetal Hematopoietic Stem and Progenitor Cells Through Altered Inflammatory Signaling

BackgroundMaternal obesity is a global health challenge with profound consequences for offspring health. While its impact on metabolic programming has been widely studied, far less is known about how maternal obesity shapes the fetal immune system. The fetal bone marrow (FBM) is the central site of hematopoietic stem and progenitor cell (HSPC) development, and disruptions in this niche can have lifelong effects on immunity, infection susceptibility, and inflammatory disease risk. In this study, we examined FBM hematopoiesis in a nonhuman primate model of spontaneous maternal obesity. MethodsUsing spectral flow cytometry, single-cell RNA sequencing, and functional differentiation assays, we mapped progenitor composition, lineage trajectories, and immune function in offspring exposed to maternal obesity compared with lean controls. These complementary approaches allowed us to capture cellular frequencies and transcriptional programs, while trajectory and signaling analyses provided insight into how progenitor maturation and intercellular communication are disrupted by maternal obesity. ResultsOur findings reveal that maternal obesity decreases CD34+ HSPCs and common lymphoid progenitor populations, while expanding megakaryocyte-erythroid and granulocyte-monocyte progenitors. Pseudotime analysis demonstrated altered maturation, with cells accumulating at early differentiation states. Transcriptional profiling uncovered a strong inflammatory bias, with myeloid progenitors upregulating alarmins, interferon-stimulated genes, and proinflammatory mediators. Functionally, monocytes derived from obese FBM showed impaired migratory and colony-stimulating capacity, coupled with exaggerated TNF responses to LPS stimulation. ConclusionTogether, these results demonstrate that maternal obesity, even in the absence of obesogenic diet, disrupts fetal bone marrow hematopoiesis by altered HSPC maturation, reprogramming lineage trajectories, and inducing inflammatory bias.

immunology↗

bioRxiv2025

Chronic alcohol consumption enhances the differentiation capacity of hematopoietic stem and progenitor cells into osteoclast precursors

Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. We have previously shown using a rhesus macaque model of voluntary ethanol consumption that CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them towards a hyper-inflammatory response. Here, we extended those studies and investigated alterations in osteoclasts, which, in postnatal life, are differentiated from HSPCs and play a critical role in maintaining bone homeostasis. Analysis using spectral flow cytometry revealed a skewing of HSPCs towards granulocyte-monocyte progenitors (GMPs) with the CAC group that was in concordance with an increased number of colony-forming unit-granulocyte/macrophage (CFU-GM). Additionally, HSPCs from animals in the CAC group incubated with M-CSF and RANKL were more likely to differentiate into osteoclasts, as evidenced by increased Tartrate-Resistant Acid Phosphatase (TRAP) staining and bone resorption activity. Moreover, single-cell RNA sequencing of differentiated HSPCs identified three clusters of osteoclast precursors in the CAC group with enhanced gene expression in pathways associated with cellular response to stimuli, membrane trafficking, and vesicle-mediated transport. Collectively, these data show that CAC-derived hematopoietic progenitor cells exhibit a higher capacity to differentiate into osteoclast precursors. These findings provide critical insights for future research on the mechanisms by which CAC disrupts monopoiesis homeostasis and enhances osteoclast precursors, thereby contributing to reduced bone density.

cell biology↗

bioRxiv2025

Phenotypic and Functional Alterations in Peripheral Blood Mononuclear Cell-Derived Microglia in a Primate Model of Chronic Alcohol Consumption

Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from non-human primates (NHP) into microglia-like cells (induced-microglia; iMGL). The iMGLs displayed transcriptional profiles distinct from those of monocyte progenitors and closely resembling those of primary microglia. Notably, morphological features showed that differentiated iMGLs derived from NHPs with chronic alcohol consumption (CAC) possessed a more mature-like microglial morphology. Additionally, dysregulation in key inflammatory and regulatory markers alongside increased baseline phagocytic activity was observed in CAC-derived IMGLs in the resting state. Phenotypic and functional assessments following LPS stimulation indicated the presence of an immune-tolerant phenotype and enrichment of a CD86+ hyper-inflammatory subpopulation in iMGLs derived from ethanol-exposed animals. Collectively, these findings demonstrate that in vitro differentiation of PBMC offers a minimally invasive approach to studying the impact of CAC on microglial function revealing that CAC reshapes both functional and transcriptional profiles of microglia.

neuroscience↗