CRISPER/cas9-Human Germline Gene Editing: Study of Islamic Ethical and Scientific Perspectives

The advancement of technology in medical science has just changed human lives, as well as biomedical innovations are making human lives better but lesser harmful. In past, scientifically and religiously approved techniques such as testtube baby & human stem cells therapy have served humanity especially infertile and connubial parents. Nowadays, the advancement in CRISPER/cas9 technology which is about human germline gene editing, just rekindled the religious and ethical concerns, especially in Islamic perspectives. Although, human germline genome editing and modification have been started decades ago claims about disease prevention strategies have raised many religious concerns such as tampering with God’s creation, human dignity, safety and efficacy of the technology, and human genetic enhancement. This kind of editing might result in inheritable changes in the human genome. So, questions about its status whether it should be allowed or not, need deep & serious study from religious and ethical perspectives. This study will encompass Islamic perspectives on these concerns in the light of ethical principles of Islam while considering and assessing the permissibility or lawful status of CRISPR/Cas9 mediated human germline gene editing. This research study also aims to address the controversial discussions among Muslim jurists regarding human germline gene editing as well as to comprise the related ethical regulations and concerns.

Development of a novel embryonic germline gene-related prognostic model of lung adenocarcinoma

Background Emerging evidence implicates the correlation of embryonic germline genes with the tumor progress and patient’s outcome. However, the prognostic value of these genes in lung adenocarcinoma (LUAD) has not been fully studied. Here we systematically evaluated this issue, and constructed a novel signature and a nomogram associated with embryonic germline genes for predicting the outcomes of lung adenocarcinoma. Methods The LUAD cohorts retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used as training set and testing set, respectively. The embryonic germline genes were downloaded from the website https://venn.lodder.dev. Then, the differentially expressed embryonic germline genes (DEGGs) between the tumor and normal samples were identified by limma package. The functional enrichment and pathway analyses were also performed by clusterProfiler package. The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. Survival and Receiver Operating Characteristic (ROC) analyses were performed to validate the model using training set and four testing GEO datasets. Finally, a prognostic nomogram based on the signature genes was constructed using multivariate regression method. Results Among the identified 269 DEGGs, 249 were up-regulated and 20 were down-regulated. GO and KEGG analyses revealed that these DEGGs were mainly enriched in the process of cell proliferation and DNA damage repair. Then, 103 DEGGs with prognostic value were identified by univariate Cox regression and further filtered by LASSO method. The resulting sixteen DEGGs were included in step multivariate Cox regression and an eleven embryonic germline gene related signature (EGRS) was constructed. The model could robustly stratify the LUAD patients into high-risk and low-risk groups in both training and testing sets, and low-risk patients had much better outcomes. The multi-ROC analysis also showed that the EGRS model had the best predictive efficacy compared with other common clinicopathological factors. The EGRS model also showed robust predictive ability in four independent external datasets, and the area under curve (AUC) was 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094). More importantly, the expression level of some genes in EGRS has a significant correlation with the progression of LUAD clinicopathology, suggesting these genes might play an important role in the progression of LUAD. Finally, based on EGRS genes, we built and calibrated a nomogram for conveniently evaluating patients’ outcomes.

Intercellular transport of RNA can limit heritable epigenetic changes

RNAs in circulation carry sequence-specific regulatory information between cells in animal, plant, and host-pathogen systems. Double-stranded RNA (dsRNA) delivered into the extracellular space of the nematode C. elegans accumulates within the germline and reaches progeny. Here we provide evidence for spatial, temporal, and substrate specificity in the transport of dsRNA from parental circulation to progeny. Temporary loss of dsRNA transport resulted in the persistent accumulation of mRNA from a germline gene. The expression of this gene varied among siblings and even between gonad arms within one animal. Perturbing RNA regulation of the gene created new epigenetic states that lasted for many generations. Thus, one role for the transport of dsRNA into the germline in every generation is to limit heritable changes in gene expression.One Sentence SummaryRNA from parental circulation reduces heritable changes in gene expression.

A global chromatin compaction pathway that represses germline gene expression during starvation

While much is known about how transcription is controlled at individual genes, comparatively little is known about how cells regulate gene expression on a genome-wide level. Here, we identify a molecular pathway in the C. elegans germline that controls transcription globally in response to nutritional stress. We report that when embryos hatch into L1 larvae, they sense the nutritional status of their environment, and if food is unavailable, they repress gene expression via a global chromatin compaction (GCC) pathway. GCC is triggered by the energy-sensing kinase AMPK and is mediated by a novel mechanism that involves the topoisomerase II/condensin II axis acting upstream of heterochromatin assembly. When the GCC pathway is inactivated, then transcription persists during starvation. These results define a new mode of whole-genome control of transcription.

Alternative somatic and germline gene-regulatory strategies during starvation-induced developmental arrest

Nutrient availability governs growth and quiescence, and many animals arrest development when starved. Somatic and germline cells have distinct functions and constraints, suggesting different regulatory mechanisms contribute to an integrated starvation response. Using C. elegans L1 arrest as a model, we show that gene expression changes deep into starvation. Surprisingly, relative expression of germline-enriched genes increases for days. We conditionally degraded the large subunit of RNA Polymerase II and found that early but not late somatic transcription is required for survival and that germline transcription does not affect survival. Expression analysis revealed that thousands of genes are continuously transcribed in the soma, though their absolute abundance declines, while the germ line is transcriptionally quiescent with extreme transcript stability. This work reveals alternative somatic and germline gene-regulatory strategies during starvation, with the soma relying on a robust transcriptional response to support immediate survival while the germ line relies on transcriptional quiescence and mRNA stability to maintain future reproductive success.