Project description:LSCs have been clinically approved as a cell therapy to treat limbal stem cell deficiency (LSCD), however, there has yet to be a consensus on LSC markers that allow the isolation of LSCs, and their transcriptome profile is not fully understood. In this study, we addressed this problem by using single nuclei RNA sequencing (snRNAseq) on healthy human limbal tissue excised from cataract patients.
Project description:Abnormalities in neocortical and synaptic development have been associated with neurodevelopmental disorders. However, the molecular and cellular mechanisms regulating the formation of the initial synapses in an evolutionary advanced neocortical layer, the subplate (SP), are poorly understood. Our snRNAseq screen of human prefrontal neocortices from early (11/12 PCW), mid (14/15 PCW) to late (17/18 PCW) fetal developmental stages revealed the bipartite-to-tripartite differentiation of SP neuronal subclasses. Using polysome profiling with RNAseq, we report for the first time a set of mRNAs undergoing translational control in cellular subclasses of developing human prefrontal neocortices, including SP neurons. By examining both mouse and human neocortex, we further found that an autism spectrum disorder (ASD)-risk gene and RNA binding protein CUGBP Elav-Like Family Member 4 (CELF4) is selectively expressed in the neurons of two synapse-enriched compartments, the SP and the marginal zone. Furthermore, CELF4 binds mRNA targets that are encoded by the synaptic genes associated with ASD and adverse neurodevelopmental outcomes; albeit in an evolutionarily advanced fashion between mouse and human synaptic mRNAs. The selective forebrain Celf4 deletion from developing mouse cortical neurons disrupts the balance of SP synapses in a gender-specific fashion. Taken together, our results underscore the importance of RNA binding proteins and mRNA translation in evolutionarily advanced synaptic development, as well as their possible contribution to gender specific protein synthesis and vulnerability.
Project description:To investigate the development of aldosterone-producing adenoma, we profiled cells of different areas of the adjacent adrenal cortex by snRNAseq to obtain possible trajectories towards adenoma formation.