Publications

Suspension culture in a rotating bioreactor for efficient generation of human intestinal organoids

Human intestinal organoids (HIOs) derived from human pluripotent stem cells (hPSCs) hold great promise for translational medical applications. A common method to obtain HIOs has been to harvest floating hindgut spheroids arising from hPSCs. As this technique is elegant but burdensome due to the complex protocol and line-to-line variability, a more feasible method is desired. Here, we establish a robust differentiation method into suspension-cultured HIOs (s-HIOs) by seeding dissociated cells on a spheroid-forming plate.

Fluorescence-Activated Nuclei Negative Sorting of Neurons Combined with Single Nuclei RNA Sequencing to Study the Hippocampal Neurogenic Niche

Adult Hippocampal Neurogenesis (AHN), which consists of a lifelong maintenance of proliferative and quiescent neural stem cells (NSCs) within the sub-granular zone (SGZ) of the dentate gyrus (DG) and their differentiation from newly born neurons into granule cells in the granule cell layer, is well validated across numerous studies. Using genetically modified animals, particularly rodents, is a valuable tool to investigate signaling pathways regulating AHN and to study the role of each cell type that compose the hippocampal neurogenic niche.

HIV fragments detected in Kaposi sarcoma tumor cells in HIV-infected patients

Kaposi sarcoma (KS) is a malignant vascular neoplasm caused by KS-associated herpesvirus (KSHV) infection. HIV plays a major role in KS pathogenesis. KS in HIV usually produces more malignant features than classic KS. Despite the close KS-HIV relationship, no study has reported the existence of HIV in KS tissue. We used ddPCR to detect HIV and KSHV in HIV+ KS samples and classic KS control. We verified KS cell types through immunohistochemistry and applied hypersensitive in situ hybridization (ISH) to detect HIV and KSHV in tumor cells.

A Murine Calvarial Defect Model for the Investigation of the Osteogenic Potential of Fetal Umbilical Cord Stem Cells in Alveolar Cleft Repair

Background: The standard graft material for alveolar cleft repair (ACR) is autogenous iliac crest. However, a promising alternative potential graft adjunct - newborn human umbilical cord mesenchymal stem cells (h-UCMSC) - has yet to be explored in vivo. Their capacity for selfrenewal, multipotent differentiation, and proliferation allows h-UCMSC to be harnessed for regenerative medicine. Our study seeks to evaluate the efficacy of using tissue-derived hUCMSC and their osteogenic capabilities in a murine model to improve ACR.

In situ sequence-specific visualization of single methylated cytosine on tissue sections using ICON probe and rolling-circle amplification

Since epigenetic modifications differ from cell to cell, detecting the DNA methylation status of individual cells is requisite. Therefore, it is important to conduct "morphology-based epigenetics research", in which the sequence-specific DNA methylation status is observed while maintaining tissue architecture. Here we demonstrate a novel histochemical technique that efficiently shows the presence of a single methylated cytosine in a sequence-dependent manner by applying ICON (interstrand complexation with osmium for nucleic acids) probes.

The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut

The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at the base of intestinal crypts. The signal transduction pathways and morphogens that regulate intestinal stem cell self-renewal and differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part of the intestinal stem cell niche, their direct influence on the cellular composition is less well understood.

Localization and characterization of Proenkephalin-A as a potential biomarker for kidney disease in murine and human kidneys

IntroductionExact measurement of renal function is essential for the treatment of patients. Elevated serum-creatinine levels, while established are influenced by other parameters and show a significant time-lag. This drives the search for novel biomarkers of renal function and injury. Beside Lipocalin-2 and kidney-injury-molecule-1(KIM-1), the endogenous opioid precursor proenkephalin-A(Penk) has recently emerged as a promising marker for renal function.

Association of sarcoidosis with psoriasis: a cross-sectional study in the All of Us research program

Psoriasis and sarcoidosis are inflammatory skin and systemic diseases that may share a similar immunopathogenesis involving a Th1 and/or Th17 polarized immune response. Although the coexistence of sarcoidosis and psoriasis in the same individuals has been reported, the potential association between these diseases at a population-level in the United States has not been evaluated. To evaluate this association, we performed a matched cross-sectional study in the All of Us research program database.

Neurotransmitter phenotype and axonal projection patterns of VIP-expressing neurons in the inferior colliculus

Neurons in the inferior colliculus (IC), the midbrain hub of the central auditory pathway, send ascending and descending projections to other auditory brain regions, as well as projections to other sensory and non-sensory brain regions. However, the axonal projection patterns of individual classes of IC neurons remain largely unknown. Vasoactive intestinal polypeptide (VIP) is a neuropeptide expressed by subsets of neurons in many brain regions.

Formation of the glomerular microvasculature is regulated by VEGFR-3

Microvascular dysfunction is a key driver of kidney disease. Pathophysiological changes in the kidney vasculature are regulated by vascular endothelial growth factor receptors (VEGFRs), supporting them as potential therapeutic targets. The tyrosine kinase receptor VEGFR-3, encoded by FLT4, and activated by the ligands VEGF-C and VEGF-D, is best known for its role in lymphangiogenesis. Therapeutically targeting VEGFR-3 to modulate lymphangiogenesis has been proposed as a strategy to treat kidney disease.

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