4 documents found, page 1 of 1
Epigenetics and genetics of hematopoietic stem cells heterogeneity
Kubasova, NadiyaAbstract In diploid eukaryotic organisms, most genes are expressed biallelically. However, there are exceptions where the expression occurs in a monoallelic pattern that results from a differential allele-specific transcription based on the different epigenetic marking of the two alleles. At the level of cells, there are three classes of monoallelic expression regulated by epigenetic mechanisms: parent-of-origi...
In vivo clonal analysis reveals random monoallelic expression in lymphocytes th...
Kubasova, Nadiya; Alves-Pereira, Clara F.; Gupta, Saumya; Vinogradova, Svetlana; Gimelbrant, Alexander; Barreto, Vasco M.Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess the cells’ heterogeneity and predict their fate. Here, using a genome-wide transcriptomics approach in vivo, we evaluated the allelic expression imbalance in the progeny of single hematopoietic cells (HSCs) as a read-out of epigenetic marking. After 4 months of extensive proliferation and differentia...
Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascu...
Mahú, Inês; Barateiro, Andreia; Rial-Pensado, Eva; Martinéz-Sánchez, Noelia; Vaz, Sandra H.; Cal, Pedro M.S.D.; Jenkins, Benjamin; Rodrigues, Tiago M.Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PE...
A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral ce...
Pereira, Mafalda M. A.; Mahú, Inês; Seixas, Elsa; Martinéz-Sánchez, Noelia; Kubasova, Nadiya; Pirzgalska, Roksana M; Cohen, Paul; Dietrich, Marcelo OConditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood-brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic a...