Transcriptional and Cellular Response of hiPSC-derived Microglia-Neural Progenitor Co-Cultures Exposed to IL-6 DOI Creative Commons
Amalie C.M. Couch,

Amelia M. Brown,

Catarina Raimundo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 22, 2023

Abstract Elevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool study effects of IL-6 on features relevant human neurodevelopment vitro . We previously reported that hiPSC-derived microglia-like cells (MGLs) respond IL-6, neural progenitor (NPCs) monoculture do not. Therefore, we investigated whether co-culturing MGLs with NPCs would trigger cellular response stimulation via secreted factors from MGLs. Using N=4 donor lines without psychiatric diagnosis, first confirmed can through trans-signalling when recombinant IL-6Ra is present, and this dose-dependent. soluble IL-6R, at lower than found vivo below needed activate NPCs. Whilst transcriptomic secretome analysis undergo substantial changes after exposure subsequently secrete cytokine milieu, co-culture exhibited minimal transcriptional response. Furthermore, there were no significant fate-acquisition differentiated into post-mitotic cultures, nor alterations synaptic densities mature neurons. These findings highlight need investigate if trans-IL-6 signalling disease linking disorders. Moreover, our underscore importance establishing more complex diverse types, which may show cell-specific responses microglia-released cytokines fully understand how influence neurodevelopment.

Language: Английский

An investigation on the alterations in Wnt signaling in ADHD across developmental stages DOI Creative Commons

Natalie Monet Walter,

Cristine Marie Yde Ohki,

Michelle Rickli

et al.

Neuroscience Applied, Journal Year: 2024, Volume and Issue: 3, P. 104070 - 104070

Published: Jan. 1, 2024

The canonical Wnt signaling pathway plays a vital role in the developmental processes of Central Nervous System throughout both prenatal and postnatal stages, as well maintaining homeostasis during adulthood. Its complex intracellular cascade involves participation key proteins (i.e., GSK3β β-catenin) to activate transcription target genes. These genes subsequently control like cell proliferation, maturation, determination fate. Previous studies suggest that this can also be associated with Attention-Deficit Hyperactivity Disorder (ADHD), neurodevelopmental disorder multifactorial etiology. This study aimed clarify if at what stage is altered ADHD. Accordingly, we carried out proteomic functional assessments using Western Blot reporter assays, respectively. were performed induced pluripotent stem (iPSC), neural (NSC), neuronal phases. IPSCs generated from somatic cells retrieved 5 controls patients diagnosed As opposed iPSCs, ADHD NSCs showed alterations protein expression β-catenin, suggesting increased activity group. Moreover, assays confirmed higher NSCs. Our molecular findings correlated genetic predisposition clinical traits displayed by their respective donors. In conclusion, these results crucial cellular disrupted patient-specific NSCs, potentially explaining deficits clinically exhibited patients.

Language: Английский

Citations

4
Alterations in proliferation of neuronal stem cells in Attention-Deficit/Hyperactivity Disorder and Wnt modulation by methylphenidate DOI Creative Commons
Edna Grünblatt, Cristine Marie Yde Ohki,

Natalie Monet Walter

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Abstract As the most common neurodevelopmental and mental disorders around world, attention-deficit/hyperactivity disorder (ADHD) affects mostly children adolescents. Both genetic (polygenicity) environmental variables interplay in etiology of this disorder. The Wnt signaling pathway, which regulates proliferation differentiation during neurodevelopment, has been implicated ADHD. Clinically, ADHD individuals may exhibit delays structural functional brain development. Available evidence proposed that methylphenidate (MPH) treatment can potentially improve these delays. However, molecular cellular mechanisms underlying therapeutic targets MPH are still not completely elucidated. In a pilot investigation, neural stem cells (NSCs) derived from induced pluripotent (iPSCs) was significantly lowered male patients. Yet, we did observe any variations growth rates iPSC stage. To extend earlier results, increased sample size to include females explored if NSC clarified role pathway. do so, five patients controls assessed. results corroborated our previous findings on decreased NSCs. Conversely, slightly following at 10 nM, also showed modulatory effects group. Interestingly, no increases were seen when DKK1 blocked before treatment. These suggest canonical pathway partially explain abnormalities MPH-specific benefits.

Language: Английский

Citations

0
Defined culture conditions robustly maintain human stem cell pluripotency, highlighting a role for Ca2+ signaling DOI Creative Commons
Ilse Eidhof, Benjamin Ulfenborg,

Malin Kele

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 18, 2025

Abstract Induced pluripotent stem cells (iPSCs) have significant potential for disease modeling and cell therapies. However, their wide-spread application has faced challenges, including batch-to-batch variabilities, notable distinctions when compared to embryonic (ESCs). Some of these disparities can from using undefined culture conditions the reprogramming procedure, however, precise mechanisms remain understudied. Here, we gene expression data over 100 iPSC ESC lines cultivated under defined conditions. Defined significantly reduced inter-PSC line variability, irrespective PSC type, highlighting importance standardization minimize biases. This variability is concurrent with decreased somatic marker germ layer differentiation increased Ca 2+ -binding protein expression. Moreover, SERCA pump inhibition highlighted an important role intracellular activity in maintaining pluripotency Further understanding processes help standardize improve hPSC

Language: Английский

Citations

0
Race and ethnicity matter! Moving Parkinson’s risk research towards diversity and inclusiveness DOI Creative Commons
Sara Siddiqi,

Z Ortiz,

Stephanie Simard

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 7, 2025

Language: Английский

Citations

0
Navigating pharmaceuticals: microfluidic devices in analytical and formulation sciences DOI Creative Commons

Ankita Das,

Parixit Prajapati

Discover Chemistry., Journal Year: 2025, Volume and Issue: 2(1)

Published: March 22, 2025

Language: Английский

Citations

0
A new dawn: Vitalising translational oncology research in Africa with the help of advanced cell culture models DOI
Stefanie Klima, Tracey Hurrell, Mubeen Goolam

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 56, P. 102391 - 102391

Published: April 14, 2025

Language: Английский

Citations

0
Neuropharmacology in the Molecular Epoch DOI

Neelakanta Sarvashiva Kiran,

Chandrashekar Yashaswini,

Bhupendra G. Prajapati

et al.

Published: April 17, 2025

Language: Английский

Citations

0
Cortisol-dependent impairment of dendrite plasticity in human dopaminergic neurons derived from hiPSCs is restored by ketamine: Relevance for major depressive disorders. DOI Creative Commons

Laura Cavalleri,

Irene Dassieni,

G.S. Marcotto

et al.

Neuroscience Applied, Journal Year: 2024, Volume and Issue: 3, P. 104049 - 104049

Published: Jan. 1, 2024

Impaired neuroplasticity in neurons endowed limbic circuits is considered a hallmark of chronic stress and depression. The reasons for this impairment are still partially unclear, but converging findings suggest that it can be reverted by exposure to rapid-acting antidepressants. In study we revamped the hypothesis abnormal high circulating levels cortisol observed Major Depressive Disorders with anhedonia may contribute drive circuit impairment. Here used an established in-vitro translational model based on human iPSC-derived dopaminergic extend evidence obtained rodents glucocorticoid-induced hypotrophy cortical dendrites. predictive value was tested assessing reversal potential antidepressants cortisol-induced hypotrophy. Human mesencephalic were differentiated from healthy donor iPSCs 60–70 days. Cortisol effects assessed measuring maximal dendrite length, primary number soma area 3 days after last exposure. Concentration- time-response curves initially established. produced concentration- time-dependent reduction dendritic arborization neurons, at 50 μM 4-day dosing. These when followed 1-hr ketamine or (2R,6R)-hydroxynorketamine concentrations 0.01 0.05 μM, respectively, resulting approximately 10- 100-fold lower than those effective not exposed cortisol. Overall, impaired sensitized their response very low doses known upregulate AMPA-mediated glutamatergic neurotransmission.

Language: Английский

Citations

3
Correspondence to “Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca2+ entry and accelerated differentiation” by Hewitt et al. (PMID: 37402854) DOI
Cristine Marie Yde Ohki, Rhiannon V. McNeill, Anthony C. Vernon

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(12), P. 3932 - 3934

Published: May 24, 2024

Language: Английский

Citations

1
Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis DOI Creative Commons
Bálint Jezsó, János Kálmán, K Farkas

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 688 - 688

Published: June 13, 2024

Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine effects of typical atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation neurite outgrowth were measured by live imaging, gene expression levels related identity analyzed RT-QPCR immunocytochemistry during into hippocampal dentate gyrus granule following treatment low- high-dose (haloperidol, olanzapine, risperidone). Results: Antipsychotics did not modify growth properties NPCs after 3 days treatment. However, characteristics changed significantly in response haloperidol olanzapine. After three weeks differentiation, mRNA selected markers increased (except MAP2), while caused only subtle changes. Additionally, we found no changes MAP2 or GFAP protein as a result antipsychotic Conclusions: Altogether, medications promoted neurogenesis vitro influencing rather than changing survival expression. This study provides insights highlights importance considering potential target action.

Language: Английский

Citations

1