Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 16,015 nuclei in human adult testis. This dataset includes five samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
Project description:Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function. Human adult brain dissociates were sorted for one of three markers, either GLT1 (astrocyte, n =3), CD11b (microglia, n=4) or A2B5 (glial progenitor cell, n=7). In addition to positively selected, the negative fraction and unsorted dissociates were collected as matched controls for each sort.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors. Genetic deletion of either Pax6 or Brg1, the ATPase unit of the SWI/SNF complex, in neural stem cells of the adult mouse subependymal zone results in a fate conversion to distinct glial subtypes most pronounced when neuroblasts leave the neurogenic niche. Consistent with the phenocopy in vivo virtually all genes down-regulated by Brg1 deletion have Pax6-binding motifs. Amongst the few down-stream transcription factors are Sox11, Nfib and Brn4 that crossregulate each other and rescue neurogenesis also in direct reprogramming in the absence of Brg1 (or Pax6). Thus the function of Pax6-SWI/SNF is necessary and sufficient for neuronal fate maintenance and initiates a cross-regulatory effector network required for neuronal fate execution and maintenance to counteract glial differentiation in the adult brain. This identifies a novel role highly specific role of a chromatin-remodelling complex in stabilizing fate decisions in normal and forced neurogenesis. We performed gene expression microarray analysis on tissue derived from the SEZ or from the core region of the olfactory bulb from Brg1 cKO and control mice
Project description:Development of T-cells provides a unique opportunity to study cell-fate determination due to the accessability and the well defined stages of developmental stages. In order to understand the genetic programs underlying fetal and adult T‑cell fate specification we subjected highly purified fetal and adult T-cell progenitor populations to a genome‑wide transcriptional analysis. The aim was to identify molecular elements that govern T-cell fate specification as a whole but ultimately to isolate elements that were specific for a given population in a specific developmental window. FACS purified ETP, DN2 and DN3 progenitor thymocytes from C57BL/6 adult mice and E14.5 embryos were hybridised to Affymetrix Mouse Genome 430A_2.0 GeneChip Arrays.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6
Project description:Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrogenic programs while inhibiting Stat3-mediated astrogliogenesis, and thereby regulate phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. Examination of Hdac3 and p300 genomewide occupancy in differentiating oligodendrocytes