Pluto Bioinformatics

GSE126914: Transcriptome-wide analysis of long and short RNAs in mouse embryonic stem cells (ESC) and differentiated cells depleted of a functional Htt gene

Bulk RNA sequencing

The HTT gene mutated in Huntingtons Disease (HD) has essential roles during normal development. However, still not fully understood are the functional consequences of its partial inactivation. Our genetic study provides a comprehensive description of the effects of progressively more severe decreases in expression of Htt, the murine HTT counterpart. The most severe Htt decrease leads to lethality of early embryos, while intermediate but still severely reduced Htt dosages yield a variety of recessively inherited developmental abnormalities affecting body size, skin, skeletal and ear formation, and hematopoiesis. Comparative molecular analysis of differentiating wild-type cells and cells lacking Htt function further elucidate genes networks dysregulated during organ development. These nominate chromatin regulators and short non-coding RNAs as key molecular mediators. Together these findings demonstrate that Htt is required from conception to support normal embryonic and fetal development.; Keywords: Huntingtin, Htt, Hypomorphic mice, Pleiotropy, Mouse Embryo Development, Hematopoiesis, Skeletal - Skin - Ear Development, embryonic stem cells, neuronal progenitors, RNA and miRNA sequencing, transcriptome profiling, RNA-Seq, small RNA-Seq SOURCE: Toma Tebaldi ( - University of Trento

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