scholarly journals Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion

2020 ◽  
Vol 21 (11) ◽  
pp. 4115 ◽  
Author(s):  
Isabel Gómez-Redondo ◽  
Priscila Ramos-Ibeas ◽  
Eva Pericuesta ◽  
Raúl Fernández-González ◽  
Ricardo Laguna-Barraza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alternative Splicing ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Gene Activation ◽  
Early Embryo ◽  
Early Embryo Development ◽  
Zygotic Gene ◽  
Zygotic Gene Activation ◽  
Induced Pluripotent

Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells.

scholarly journals Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21

2017 ◽  
Author(s):  
Patrick Gonzales ◽  
Gin Fonte ◽  
Christine Roberts ◽  
Connor Jacobsen ◽  
Gretchen H. Stein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Alternative Splicing ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Repetitive Element ◽  
Chromosome 21 ◽  
Single Individual ◽  
Depth Analysis ◽  
Induced Pluripotent

AbstractTrisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In addition to characterization of gene expression levels, we have also investigated patterns of RNA adenosine-to-inosine editing, alternative splicing, and repetitive element expression, aspects of the transcriptome that have not been significantly characterized in the context of Down syndrome. We identified significant changes in transcript accumulation associated with chromosome 21 trisomy, as well as changes in alternative splicing and repetitive element transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher levels of neuronal transcripts than control disomic iPSCs, and readily differentiated into cortical neurons, in contrast to another reported study. Comparison of our transcriptome data with similar studies of trisomic iPSCs suggests that trisomy of chromosome 21 may not intrinsically limit neuronal differentiation, but instead may interfere with the maintenance of pluripotency.

scholarly journals Modeling Neurological Disorders by Human Induced Pluripotent Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Tanut Kunkanjanawan ◽  
Parinya Noisa ◽  
Rangsun Parnpai
Keyword(s):  
Stem Cells ◽  
Brain Development ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neurological Disorders ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Induced Pluripotent

Studies of human brain development are critical as research on neurological disorders have been progressively advanced. However, understanding the process of neurogenesis through analysis of the early embryo is complicated and limited by a number of factors, including the complexity of the embryos, availability, and ethical constrains. The emerging of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) has shed light of a new approach to study both early development and disease pathology. The cells behave as precursors of all embryonic lineages; thus, they allow tracing the history from the root to individual branches of the cell lineage tree. Systems for neural differentiation of hESCs and iPSCs have provided an experimental model that can be used to augmentin vitrostudies ofin vivobrain development. Interestingly, iPSCs derived from patients, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. This paper summarizes the recent reports of the development of iPSCs from patients who suffer from neurological diseases and evaluates the feasibility of iPSCs as a disease model. The benefits and obstacles of iPSC technology are highlighted in order to raising the cautions of misinterpretation prior to further clinical translations.

Directed differentiation of mouse-induced pluripotent stem cells generates dopaminergic nerve

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Induced Pluripotent

Derivation and Characterization of human Induced Pluripotent Stem Cells

Acta Naturae ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 91-92 ◽  
Author(s):  
M V Shutova ◽  
A N Bogomazova ◽  
M A Lagarkova ◽  
S L Kiselev
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

Derivation of bovine induced pluripotent stem cells by a transposon approach

2014 ◽  
Author(s):  
Talluri Thirumala Rao ◽  
Dharmendra Kumar ◽  
Silke Glage ◽  
Wiebke Garrels ◽  
Katharina Debowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent
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