Biology subjects

Pers, T.

Publications and source records attributed to Pers, T..

6 recordsLinked to original sources

bioRxiv2026

Molecularly defined subpopulations of leptin receptor neurons dissociate the control of food intake from blood pressure

While previous studies have suggested that leptin regulates cardiovascular function independently of body weight, the specific leptin receptor (Lepr)-expressing neurons that mediate these distinct effects remain unknown. We found that genes located in blood pressure (BP)-associated genome-wide association study loci were regulated by leptin in Lepr and glucagon-like peptide-1 receptor (Glp1r)-expressing (LeprGlp1r) neurons. Ablating Lepr from these cells decreased BP despite causing hyperphagic obesity. Single-cell and spatial transcriptomics revealed that LeprGlp1r neurons segregate into two distinct subpopulations of cells located in the arcuate nucleus (ARC) and dorsomedial hypothalamic nucleus (DMH). Activating ARC LeprGlp1r neurons suppressed food intake without impacting energy expenditure or cardiovascular function. Conversely, DMH LeprGlp1r neurons increased energy utilization and BP without altering food intake. Our results identify distinct LeprGlp1r neuron subpopulations that dissociate the control of food intake from outputs related to sympathetic tone, including BP, suggesting the potential therapeutic utility of targeting of these subpopulations independently.

physiology↗

bioRxiv2025

Mapping early patterning events in human neural development usingan in-vitro microfluidic stem cell model

Stem cell models can provide insights into human brain development at embryonic stages which are normally inaccessible. We previously developed the Microfluidic Stem Cell Regionalisation (MiSTR) model, which recapitulates the rostro-caudal patterning of human neural tube through a WNT activation (WNTa) gradient. Through temporal single cell transcriptomics of rostro-caudal and dorso-ventral gradient-patterned MiSTR, we found that rostro-caudal subtypes were regionally specified and fate-determined already during the late epiblast stage, several days before onset of neuralisation at day 3-4. Rostral cells were characterised by expression of HESX1 and SHISA2 during pre-neuralisation and PAX6 during early neuralisation, whereas caudal cells expressed FST and HOXA1 during pre-neuralisation and SOX1 as the dominant neuralising factor. In contrast to the early rostro-caudal specification, response to ventralisation in telencephalic progenitors was developmentally delayed and occurred around day 9. We further uncovered temporal events in human midbrain-hindbrain boundary formation and ventral forebrain patterning, contributing new knowledge on early human neural region-specification.

neuroscience↗

bioRxiv2025

A single dorsal vagal complex circuit mediates the aversive and anorectic responses to GLP1R agonists

GLP-1 receptor agonists (GLP1RAs) effectively reduce feeding to treat obesity, although nausea and other aversive side effects of these drugs can limit their use. Brainstem circuits that promote satiation and that mediate the physiologic control of body weight can be distinguished from those that cause aversion. It remains unclear whether brainstem Glp1r neurons contribute to the normal regulation of energy balance and whether GLP1RAs control appetite via circuits distinct from those that mediate aversive responses, however. Hence, we defined roles for AP and NTS Glp1r-expressing neurons (APGlp1r and NTSGlp1r neurons, respectively) in the physiologic control of body weight, the GLP1RA-dependent suppression of food intake, and the GLP1RA-mediated stimulation of aversive responses. While silencing non-aversive NTSGlp1r neurons interfered with the physiologic restraint of feeding and body weight, restoring NTSGlp1r neuron Glp1r expression on an otherwise Glp1r-null background failed to enable long-term body weight suppression by GLP1RAs. In contrast, selective Glp1r expression in APGlp1r neurons restored both aversive responses and long-term body weight suppression by GLP1RAs. Thus, while non-aversive NTSGlp1r neurons control physiologic feeding, aversive APGlp1r neurons mediate both the anorectic and weight loss effects of GLP1RAs, dictating the functional inseparability of these pharmacologic GLP1RA responses at a circuit level.

neuroscience↗

bioRxiv2019

Sandwich cortical lamination and single-cell analysis decodes the developing spatial processing system.

Classic studies investigating how and when the entorhinal cortex (component of the memory processing system of the brain) develops have been based on traditional thymidine autoradiography and histological techniques. In this study, we take advantage of modern technologies to trace at a high resolution, the cellular complexity of the developing porcine medial entorhinal cortex by using single-cell profiling. The postnatal medial entorhinal cortex comprises 4 interneuron, 3 pyramidal neuron and 2 stellate cell populations which emerge from intermediate progenitor and immature neuron populations. We discover four MGE-derived interneurons and one CGE-derived interneuron population as well as several IN progenitors. We also identify two oligodendrocyte progenitor populations and three populations of oligodendrocytes. We perform a proof-of-concept experiment demonstrating that porcine scRNA-seq data can be used to develop novel protocols for producing human entorhinal cells in-vitro. We identified six transcription factors (RUNX1A1, SOX5, FOXP1, MEF2C, TCF4, EYA2) important in neurodevelopment and differentiation from one RELN+ stellate cell population. Using a lentiviral vector approach, we reprogrammed human induced pluripotent stem cells into stellate cell-like cells which expressed RELN, SATB2, LEF1 and BCL11B. Our findings contribute to the understanding of the formation of the brains cognitive memory and spatial processing system and provides proof-of-concept for the production of entorhinal cells from human pluripotent stem cells in-vitro.

developmental biology↗

bioRxiv2019

Nationwide prediction of type 2 diabetes comorbidities

Identification of individuals at risk of developing disease comorbidities represents an important task in tackling the growing personal and societal burdens associated with chronic diseases. We employed machine learning techniques to investigate to what extent data from longitudinal, nationwide Danish health registers can be used to predict individuals at high risk of developing type 2 diabetes (T2D) comorbidities. Based on register data spanning hospitalizations, drug prescriptions and contacts with primary care contractors from >200,000 individuals newly diagnosed with T2D, we used logistic regression-, random forest- and gradient boosting models to predict five-year risk of heart failure (HF), myocardial infarction (MI), stroke (ST), cardiovascular disease (CVD) and chronic kidney disease (CKD). For HF, MI, CVD, and CKD, register-based models outperformed a reference model leveraging canonical individual characteristics by achieving area under the receiver operating characteristic curve improvements of 0.06, 0.03, 0.06, and 0.07, respectively. The top 1,000 patients predicted to be at highest risk exhibited observed incidence ratios exceeding 4.99, 3.52, 2.92 and 4.71 respectively. In summary, prediction of T2D comorbidities utilizing Danish registers led to consistent albeit modest performance improvements over reference models, suggesting that register data could be leveraged to systematically identify individuals at risk of developing disease comorbidities.

bioinformatics↗

bioRxiv2017

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

AbstractWe assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.\n\nOne Sentence SummaryWe report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.

genetics↗