The Lindstrom Lab – Kidney Organoids

Lab-specific and collaborative papers

• Dose-dependent responses to canonical Wnt transcriptional complexes in the regulation of mammalian nephron progenitors
  Development. 2024 Sep 9:dev.202279. doi: 10.1242/dev.202279. Online ahead of print. ABSTRACT In vivo and in vitro studies argue that concentration dependent Wnt signaling regulates mammalian nephron progenitor cell (NPC) programs. Canonical Wnt signaling is regulated through the stabilization of β-catenin, a transcriptional co-activator when complexed with […]
• Stepwise developmental mimicry generates proximal-biased kidney organoids
  bioRxiv [Preprint]. 2024 Jul 2:2024.06.28.601028. doi: 10.1101/2024.06.28.601028. ABSTRACT The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range of sugars, ions, and amino acids, are highly susceptible to damage, leading to pathologies necessitatin[…]
• Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease
  Cell Stem Cell. 2024 Jun 6;31(6):921-939.e17. doi: 10.1016/j.stem.2024.04.002. Epub 2024 Apr 30. ABSTRACT Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) fr[…]
• Canonical Wnt transcriptional complexes are essential for induction of nephrogenesis but not maintenance or proliferation of nephron progenitors
  bioRxiv [Preprint]. 2023 Aug 21:2023.08.20.554044. doi: 10.1101/2023.08.20.554044. ABSTRACT Wnt regulated transcriptional programs are associated with both the maintenance of mammalian nephron progenitor cells (NPC) and their induction, initiating the process of nephrogenesis. How opposing transcriptional roles are regulated remain unclear. Using an in vitr[…]
• Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids
  bioRxiv [Preprint]. 2023 May 25:2023.05.25.542343. doi: 10.1101/2023.05.25.542343. ABSTRACT Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, a[…]
• Building a kidney tree: Functional collecting duct from human pluripotent stem cells
  Dev Cell. 2022 Oct 10;57(19):2251-2253. doi: 10.1016/j.devcel.2022.09.009. ABSTRACT Human developmental studies and regenerative therapies need in vitro systems that generate cell types recapitulating mature cell physiologies. In a recent issue of Nature Biotechnology, Shi et al. (2022) show how pluripotent stem cells can differentiate into ureteric bud org[…]

The Quadrato Lab – Brain Organoids

Lab-specific and collaborative papers

• Human cerebellar organoids with functional Purkinje cells                 Cell Stem Cell. 2024;31 (1):39-51.e6. doi: 10.1016/j.stem.2023.11.013. ABSTRACT Research on human cerebellar development and disease has been hampered by the need for a human cell-based system that recapitulates the human cerebellum’s cellular diversity and functional features. Here, we report a human organoid model (human cerebellar organoids [hCerOs]) capable[…]
• Non-synaptic function of the autism spectrum disorder-associated gene SYNGAP1 in cortical neurogenesis                                                        Nat Neurosci. 2023;26 (12):2090-2103. doi: 10.1038/s41593-023-01477-3. ABSTRACT Genes involved in synaptic function are enriched among those with autism spectrum disorder (ASD)-associated rare genetic variants. Dysregulated cortical neurogenesis has been implicated as a convergent mechanism in ASD pathophysiology, yet it remains unknown how ‘synaptic’ ASD risk[…]
• Present and Future Modeling of Human Psychiatric Connectopathies With Brain Organoids                                                                                                    Biol Psychiatry. 2023;93 (7):606-615. doi: 10.1016/j.biopsych.2022.12.017. ABSTRACT Brain organoids derived from human pluripotent stem cells are emerging as a powerful tool to model cellular aspects of neuropsychiatric disorders, including alterations in cell proliferation, differentiation, migration, and lineage trajectory. To date, most contributions in the field[…]
• Not all cortical organoids are created equal                                                Nat Cell Biol. 2022;24 (6):805-806. doi: 10.1038/s41556-022-00890-3. ABSTRACT In the last decade, we have witnessed the establishment of multiple methods for deriving human cortical organoids. This study systematically compares patterning strategies and shows that combined WNT/Dual SMAD inhibition is superior to Dual SMAD inhibition in inducing robust[…]
• Autism genes converge on asynchronous development of shared neuron classes                                                                                                                 Nature. 2022;602 (7896):268-273. doi: 10.1038/s41586-021-04358-6. ABSTRACT Genetic risk for autism spectrum disorder (ASD) is associated with hundreds of genes spanning a wide range of biological functions^1-6. The alterations in the human brain resulting from mutations in these genes remain unclear. Furthermore, their phenotypic manifestation varies[…]

In Vivo Blueprints

Lab-specific and collaborative papers

• Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development
  Dev Cell. 2024 Aug 7:S1534-5807(24)00450-7. doi: 10.1016/j.devcel.2024.07.013. Online ahead of print. ABSTRACT The mammalian kidney maintains fluid homeostasis through diverse epithelial cell types generated from nephron and ureteric progenitor cells. To extend a developmental understanding of the kidney’s epithelial networks, we compared chromatin organiza[…]
• Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development
  bioRxiv [Preprint]. 2023 May 17:2023.05.16.540880. doi: 10.1101/2023.05.16.540880. ABSTRACT Mammalian kidneys maintain fluid homeostasis through the cellular activity of nephrons and the conjoined collecting system. Each epithelial network originates from distinct progenitor cell populations that reciprocally interact during development. To extend our under[…]
• A comparative study of cellular diversity between the Xenopus pronephric and mouse metanephric nephron
  Kidney Int. 2023 Jan;103(1):77-86. doi: 10.1016/j.kint.2022.07.027. Epub 2022 Aug 31. ABSTRACT The kidney is an essential organ that ensures bodily fluid homeostasis and removes soluble waste products from the organism. Nephrons, the functional units of the kidney, comprise a blood filter, the glomerulus or glomus, and an epithelial tubule that processes th[…]
• Principles of human and mouse nephron development
  Nat Rev Nephrol. 2022 Oct;18(10):628-642. doi: 10.1038/s41581-022-00598-5. Epub 2022 Jul 22. ABSTRACT The mechanisms underlying kidney development in mice and humans is an area of intense study. Insights into kidney organogenesis have the potential to guide our understanding of the origin of congenital anomalies and enable the assembly of genetic diagnostic[…]
• Modulation of GABAA receptor signaling increases neurogenesis and suppresses anxiety through NFATc4                                                                    J Neurosci. 2014;34 (25):8630-45. doi: 10.1523/JNEUROSCI.0047-14.2014. ABSTRACT Correlative evidence suggests that GABAergic signaling plays an important role in the regulation of activity-dependent hippocampal neurogenesis and emotional behavior in adult mice. However, whether these are causally linked at the molecular level remains elusive. Nuclear factor of activated T cell (NFAT) proteins[…]
• The tumor suppressor p53 fine-tunes reactive oxygen species levels and neurogenesis via PI3 kinase signaling                                                          J Neurosci. 2013;33 (36):14318-30. doi: 10.1523/JNEUROSCI.1056-13.2013. ABSTRACT Mounting evidence points to a role for endogenous reactive oxygen species (ROS) in cell signaling, including in the control of cell proliferation, differentiation, and fate. However, the function of ROS and their molecular regulation in embryonic mouse neural progenitor cells[…]
• p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury  J Neurosci. 2012;32 (40):13956-70. doi: 10.1523/JNEUROSCI.1925-12.2012. ABSTRACT Following spinal trauma, the limited physiological axonal sprouting that contributes to partial recovery of function is dependent upon the intrinsic properties of neurons as well as the inhibitory glial environment. The transcription factor p53 is involved in DNA[…]
• Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent survival of adult-born neurons and spatial memory formation in the hippocampus                                                                         Proc Natl Acad Sci U S A. 2012;109 (23):E1499-508. doi: 10.1073/pnas.1202068109. ABSTRACT New neurons generated in the adult dentate gyrus are constantly integrated into the hippocampal circuitry and activated during encoding and recall of new memories. Despite identification of extracellular signals that regulate survival and integration of adult-born neurons such as[…]

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