Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. To distinguish whether the human specific developmental pattern represent novel human-specific developmental patterns or a shift in the timing of the existing patterns, we measured mRNA expression patterns in macaque brains from prenatal to neonatal. Our results show that the major human-specific developmental patterns identified in the PFC reflects an extreme shift in timing of synaptic development. Rhesus macaque post-mortem brain samples from the superior frontal gyrus region of the prefrontal cortex were collected. Six fetal and six newborn samples were used. RNA extracted from the dissected tissue was hybridized to Affymetrix® Human Gene 1.0 ST arrays.
Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. To distinguish whether the human specific developmental pattern represent novel human-specific developmental patterns or a shift in the timing of the existing patterns, we measured mRNA expression patterns in macaque brains from prenatal to neonatal. Our results show that the major human-specific developmental patterns identified in the PFC reflects an extreme shift in timing of synaptic development.
Project description:The human brain has changed dramatically since humans diverged from our closest living relatives, chimpanzees and the other great apes. However, the genetic and developmental programs underlying this divergence are not fully understood. Here, we generate single-nucleus RNA-seq data of human, chimpanzee and macaque adult prefrontal cortex. Spatial information is obtained by isolating nuclei from sequential sections sliced from basal to apical positions. Bulk RNA-seq is performed for the same sections to determine positional information of the sections, by comparing the section transcriptome with published transcriptome data of cortical layers in human, chimpanzee and macaque.
Project description:The mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the frontline of immune defense against HIV infection. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we have performed a comparative analysis of host gene expression in the lung and GI mucosa in response to SIV infection and antiretroviral therapy. Microarrays were used to characterize changes in gene expression in the colonic, jejunal, and pulmonary (lung) mucosa that occur during chronic SIV infection in the presence or absence of antiretroviral therapy. Colon, jejunum, and lung tissues from healthy uninfected macaques and macaques with chronic stage SIV infection (+/- therapy) were used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Results: Prenatal SUL altered baseline lung genes involved in organ/cell development and grow (e.g., Ibsp, Ctsk, Igfbp5) and ARE responses (e.g., Aldh3a1, Maff, Mafg) in Nrf2+/+ neonates and in cell morphogenesis and cell death and organismal injury/abnormality inhibition (e.g., Neat1, Nox4, Vegfa, Igfbp2, Trp53) in Nrf2-/- neonates. In hyperoxia-exposed lung, prenatal SULincreased organogenesis/development genes (e.g., Prss35, Cep128) and decreased inflammatory genes (H2-D1, Cd40, Lcn2, Cdh22) in Nrf2+/+ pups. In Nrf2-/- mice exposed to hyperoxia, prenatal SFN decreased hyperoxia-upregulated many immune and inflammatory response genes (e.g., Ccl9, Btla, Ncf4, Ltb, Selplg, Csf2rb) and upregulated many DNA repair/damage checkpoint genes (e.g., Uimc1, Neil3, Nbn, Smc4, Smc6). Conclusion: Overall, prenatal maternal SUL altered genes differentially in Nrf2+/+ and Nrf2-/- lungs. However, SUL-mediated transcriptome changes affected similar biological functions benificial to host defense and organ development in both strain. Compensatory differential lung transcriptome changes in Nrf2-/- neonates may resulted in the manifest protection of their severe hyperoxic lung injury.
Project description:The mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the frontline of immune defense against HIV infection. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we have performed a comparative analysis of host gene expression in the lung and GI mucosa in response to SIV infection and antiretroviral therapy. Microarrays were used to characterize changes in gene expression in the colonic, jejunal, and pulmonary (lung) mucosa that occur during chronic SIV infection in the presence or absence of antiretroviral therapy.
Project description:We examined how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produced increased IL-5 and IL-13, were associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation was recapitulated by adoptive transfer of a fetal liver precursor following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, was associated with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a potential mechanism by which early-life inflammation results in increased asthma susceptibility, driven by hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.
Project description:To uncover the cellular architecture of the macaque ventromedial (VMH) and dorsomedial hypothalamus (DMH), we used single nucleus RNA-seq (snRNA-seq) from a Rhesus macaque
Project description:Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function and Development in a Rhesus Macaque Model