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JOURNAL ARTICLE
Maria J Knol, Raymond A Poot, Tavia E Evans, Claudia L Satizabal, Aniket Mishra, Muralidharan Sargurupremraj, Sandra van der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C Hostettler, Dianne H K van Dam-Nolen, Sander Lamballais, Mikolaj A Pawlak, Cora E Lewis, Amaia Carrion-Castillo, Theo G M van Erp, Céline S Reinbold, Jean Shin, Markus Scholz, Asta K Håberg, Anders Kämpe, Gloria H Y Li, Reut Avinun, Joshua R Atkins, Fang-Chi Hsu, Alyssa R Amod, Max Lam, Ami Tsuchida, Mariël W A Teunissen, Nil Aygün, Yash Patel, Dan Liang, Alexa S Beiser, Frauke Beyer, Joshua C Bis, Daniel Bos, R Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A M Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M Ford, Barbara Franke, Barry I Freedman, Nele Friedrich, Melissa J Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M Kamran Ikram, Clifford R Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R Knodt, Shuo Li, Keane Lim, W T Longstreth, Fabio Macciardi, Outi Mäkitie, Bernard Mazoyer, Sarah E Medland, Susumu Miyamoto, Susanne Moebus, Thomas H Mosley, Ryan Muetzel, Thomas W Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R Reay, Gennady V Roshchupkin, Reinhold Schmidt, Pamela J Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad van der Lugt, Meike W Vernooij, David J Werring, B Gwen Windham, A Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G Brunner, Quentin Le Grand, Kang Sim, Dan J Stein, Donald W Bowden, Murray J Cairns, Ahmad R Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D Calhoun, Fabrice Crivello, Lenore J Launer, Tonya White, Peter J Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J Grabe, M Arfan Ikram, Stéphanie Debette, Paul M Thompson, Sudha Seshadri, Hieab H H Adams
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants...
May 3, 2024: Cell reports medicine
#2
JOURNAL ARTICLE
Lin Lin, Jingrong Zhao, Naoto Kubota, Zhelin Li, Yi-Li Lam, Lauren P Nguyen, Lu Yang, Sheela P Pokharel, Steven M Blue, Brian A Yee, Renee Chen, Gene W Yeo, Chun-Wei Chen, Liang Chen, Sika Zheng
Mutations in human nonsense-mediated mRNA decay (NMD) factors are enriched in neurodevelopmental disorders. We show that deletion of key NMD factor Upf2 in mouse embryonic neural progenitor cells causes perinatal microcephaly but deletion in immature neurons does not, indicating NMD's critical roles in progenitors. Upf2 knockout (KO) prolongs the cell cycle of radial glia progenitor cells, promotes their transition into intermediate progenitors, and leads to reduced upper-layer neurons. CRISPRi screening identified Trp53 knockdown rescuing Upf2KO progenitors without globally reversing NMD inhibition, implying marginal contributions of most NMD targets to the cell cycle defect...
April 22, 2024: Neuron
#3
JOURNAL ARTICLE
Matthew J Buchan, Gemma Gothard, Kashif Mahfooz, Joram J van Rheede, Sophie V Avery, Alexios Vourvoukelis, Alexander Demby, Tommas J Ellender, Sarah E Newey, Colin J Akerman
The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the periphery, whereas higher-order inputs relay more complex response properties, provide contextual feedback, and modulate plasticity. Here, we reveal that a cortical neuron's higher-order input is determined by the type of progenitor from which it is derived during embryonic development. Within layer 4 (L4) of the mouse primary somatosensory cortex, neurons derived from intermediate progenitors receive stronger higher-order thalamic input and exhibit greater higher-order sensory responses...
April 26, 2024: Cell Reports
#4
REVIEW
Bryce A Manso, Alessandra Rodriguez Y Baena, E Camilla Forsberg
Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the "canonical" megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis...
April 19, 2024: Cells
#5
JOURNAL ARTICLE
Adina Sophie Graffunder, Audrey Amber Julie Bresser, Valeria Fernandez Vallone, Matthias Megges, Harald Stachelscheid, Peter Kühnen, Robert Opitz
Thyroid hormones (TH) play critical roles during nervous system development and patients carrying coding variants of MCT8 (monocarboxylate transporter 8) or THRA (thyroid hormone receptor alpha) present a spectrum of neurological phenotypes resulting from perturbed local TH action during early brain development. Recently, human cerebral organoids (hCOs) emerged as powerful in vitro tools for disease modelling recapitulating key aspects of early human cortex development. To begin exploring prospects of this model for thyroid research, we performed a detailed characterization of the spatiotemporal expression of MCT8 and THRA in developing hCOs...
April 23, 2024: Scientific Reports
#6
JOURNAL ARTICLE
Swamy R Adapa, Gregory A Hunter, Narmin E Amin, Christopher Marinescu, Andrew Borsky, Elizabeth M Sagatys, Said M Sebti, Gary W Reuther, Gloria C Ferreira, Rays Hy Jiang
All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, that is, porphyrins. We coined this essential metabolic rewiring "porphyrin overdrive" and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole-genome data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation...
July 2024: Life Science Alliance
#7
JOURNAL ARTICLE
Kruttika Phalnikar, M Srividya, S V Mythri, N S Vasavi, Archisha Ganguly, Aparajita Kumar, Padmaja S, Kishan Kalia, Srishti S Mishra, Sreeja Kumari Dhanya, Pradip Paul, Bharath Holla, Suhas Ganesh, Puli Chandramouli Reddy, Reeteka Sud, Biju Viswanath, Bhavana Muralidharan
Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects. The BD organoids show a reduction in both the number of neuroepithelial buds/cortical rosettes and the ventricular zone size...
2024: Oxf Open Neurosci
#8
JOURNAL ARTICLE
Tyler J Dause, Jiyeon K Denninger, Robert Osap, Ashley E Walters, Joshua D Rieskamp, Elizabeth D Kirby
The vasculature is a key component of adult brain neural stem cell (NSC) niches. In the adult mammalian hippocampus, NSCs reside in close contact with a dense capillary network. How this niche is maintained is unclear. We recently found that adult hippocampal NSCs express VEGF, a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that global and NSC-specific VEGF loss led to dissociation of NSCs and their intermediate progenitor daughter cells from local vasculature. Surprisingly, though, we found no changes in local vascular density...
July 2024: Life Science Alliance
#9
JOURNAL ARTICLE
Cheng Wang, Jonas Cerneckis, Yanhong Shi
Human-induced pluripotent stem cell (hiPSC) technology has enabled comprehensive human cell-based disease modeling in vitro. Due to limited accessibility of primary human neurons as well as species-specific divergence between human and rodent brain tissues, hiPSC-derived neurons have become a popular tool for studying neuronal biology in a dish. Here, we provide methods for transcription factor-driven directed differentiation of neurons from hiPSCs via a neural progenitor cell (NPC) intermediate. Doxycycline-inducible expression of neuron fate-determining transcription factors neurogenin 2 (NGN2) and achaete-scute homolog 1 (ASCL1) enables rapid and controllable differentiation of human neurons for disease modeling applications...
2024: Methods in Molecular Biology
#10
JOURNAL ARTICLE
Adil R Wani, Aisha Hamid, Gonzalo N Morales Chaya, Mubarak Hussain Syed
From insects to humans, the nervous system generates complex behaviors mediated by distinct neural circuits that are composed of diverse cell types. During development, the spatiotemporal gene expression of the neural progenitors expands the diversity of neuronal and glial subtypes. Various neural stem cell-intrinsic and -extrinsic gene programs have been identified that are thought to play a major role in generating diverse neuronal and glial cell types. Drosophila has served as an excellent model system for discovering the fundamental principles of nervous system development and function...
April 15, 2024: Cold Spring Harbor Protocols
#11
JOURNAL ARTICLE
Gonzalo N Morales Chaya, Aisha Hamid, Adil R Wani, Andrew Gutierrez, Mubarak Hussain Syed
Complex behaviors are mediated by a diverse class of neurons and glia produced during development. Both neural stem cell-intrinsic and -extrinsic temporal cues regulate the appropriate number, molecular identity, and circuit assembly of neurons. The Drosophila central complex (CX) is a higher-order brain structure regulating various behaviors, including sensory-motor integration, celestial navigation, and sleep. Most neurons and glia in the adult CX are formed during larval development by 16 Type II neural stem cells (NSCs)...
April 15, 2024: Cold Spring Harbor Protocols
#12
JOURNAL ARTICLE
Qinglin Fei, Doo Soon Im, Yiwen Xu, Tianwen Huang, Dianbo Qu
The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear...
2024: Frontiers in Cell and Developmental Biology
#13
JOURNAL ARTICLE
Amélie Roehrig, Theo Z Hirsch, Aurore Pire, Guillaume Morcrette, Barkha Gupta, Charles Marcaillou, Sandrine Imbeaud, Christophe Chardot, Emmanuel Gonzales, Emmanuel Jacquemin, Masahiro Sekiguchi, Junko Takita, Genta Nagae, Eiso Hiyama, Florent Guérin, Monique Fabre, Isabelle Aerts, Sophie Taque, Véronique Laithier, Sophie Branchereau, Catherine Guettier, Laurence Brugières, Brice Fresneau, Jessica Zucman-Rossi, Eric Letouzé
Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions...
April 8, 2024: Nature Communications
#14
REVIEW
Taeyoung Ahn, Eun-Ah Bae, Hyungseok Seo
T cell exhaustion, which is observed in various chronic infections and malignancies, is characterized by elevated expression of multiple inhibitory receptors, impaired effector functions, decreased proliferation, and reduced cytokine production. Notably, while adoptive T cell therapies, such as chimeric antigen receptor (CAR)-T therapy, have shown promise in treating cancer and other diseases, the efficacy of these therapies is often compromised by T cell exhaustion. It is imperative, therefore, to understand the mechanisms underlying this exhaustion to promote advances in T cell-related therapies...
April 5, 2024: Molecular Therapy
#15
JOURNAL ARTICLE
Frédérique Clément, Jules Olayé
We have designed a stochastic model of embryonic neurogenesis in the mouse cerebral cortex, using the formalism of compound Poisson processes. The model accounts for the dynamics of different progenitor cell types and neurons. The expectation and variance of the cell number of each type are derived analytically and illustrated through numerical simulations. The effects of stochastic transition rates between cell types, and stochastic duration of the cell division cycle have been investigated sequentially. The model does not only predict the number of neurons, but also their spatial distribution into deeper and upper cortical layers...
March 30, 2024: Mathematical Biosciences
#16
JOURNAL ARTICLE
Maria Cristina Vinci, Sarah Costantino, Giulia Damiano, Erica Rurali, Raffaella Rinaldi, Vera Vigorelli, Annalisa Sforza, Ermes Carulli, Sergio Pirola, Giorgio Mastroiacovo, Angela Raucci, Assam El-Osta, Francesco Paneni, Giulio Pompilio
BACKGROUND: Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny. METHODS AND RESULTS: High glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokines TNFα and IL6...
March 29, 2024: Cardiovascular Diabetology
#17
JOURNAL ARTICLE
Laure Coquand, Clarisse Brunet Avalos, Anne-Sophie Macé, Sarah Farcy, Amandine Di Cicco, Marusa Lampic, Ryszard Wimmer, Betina Bessières, Tania Attie-Bitach, Vincent Fraisier, Pierre Sens, Fabien Guimiot, Jean-Baptiste Brault, Alexandre D Baffet
The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids. Through the live analysis of hundreds of dividing progenitors, we show that basal radial glial cells undergo abundant symmetric amplifying divisions, and frequent self-consuming direct neurogenic divisions, bypassing intermediate progenitors...
March 28, 2024: Nature Cell Biology
#18
JOURNAL ARTICLE
Bhargav D Sanketi, Madhav Mantri, Liqing Huang, Mohammad A Tavallaei, Shing Hu, Michael F Z Wang, Iwijn De Vlaminck, Natasza A Kurpios
Inside the finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic capillary, the lacteal, sending fats into the systemic blood circulation for energy production. Despite this vital function, mechanisms of formation, assembly alongside lacteals, and maintenance of villus smooth muscle are unknown. By combining single-cell RNA sequencing and quantitative lineage tracing of the mouse intestine, we identified a local hierarchy of subepithelial fibroblast progenitors that differentiate into mature smooth muscle fibers via intermediate contractile myofibroblasts...
March 19, 2024: Developmental Cell
#19
REVIEW
Hisato Kondoh, Tatsuya Takemoto
Neuromesodermal progenitors (NMPs), serving as the common origin of neural and paraxial mesodermal development in a large part of the trunk, have recently gained significant attention because of their critical importance in the understanding of embryonic organogenesis and the design of in vitro models of organogenesis. However, the nature of NMPs at many essential points remains only vaguely understood or even incorrectly assumed. Here, we discuss the nature of NMPs, focusing on their dynamic migratory behavior during embryogenesis and the mechanisms underlying their neural vs...
March 21, 2024: Cells
#20
JOURNAL ARTICLE
Michaela Wilsch-Bräuninger, Jula Peters, Wieland B Huttner
The development of the neocortex involves an interplay between neural cells and the vasculature. However, little is known about this interplay at the ultrastructural level. To gain a 3D insight into the ultrastructure of the developing neocortex, we have analyzed the embryonic mouse neocortex by serial block-face scanning electron microscopy (SBF-SEM). In this study, we report a first set of findings that focus on the interaction of blood vessels, notably endothelial tip cells (ETCs), and the neural cells in this tissue...
2024: Frontiers in Cell and Developmental Biology
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