Rolando, C. | bioRxiv Science

bioRxiv2021

Safb1 regulates cell fate determination in adult neural stem cells by enhancing Drosha cleavage of NFIB mRNA

During brain homeostasis, stem cell fate determination is crucial to guarantee function, adaptation and regeneration while preventing neurodegeneration and cognitive impairment. How neural stem cells (NSCs) are instructed to generate neurons or glia is not well understood. Here we addressed how fate is resolved in multipotent adult hippocampal NSCs, and identify Scaffold Attachment Factor B1 (Safb1) as a determinant of neuron production by blocking glial commitment. Safb1 is sufficient to block oligodendrocytic differentiation of NSCs by preventing expression of the transcription factor NFIB at the post-transcriptional level. Detailed interrogation of the Drosha interactome and functional validation revealed that Safb1 enhances NFIB mRNA cleavage in a Drosha-dependent fashion. Thus, our study provides a cellular mechanism for selective NSC fate regulation by post-transcriptional destabilization of mRNAs. Given the importance of NSC maintenance and fate determination in the adult brain, our findings have major implications for cell-specific gene expression, brain disease and aging.

neuroscience↗

bioRxiv2020

Extinct species identification from Upper Pleistocene bone fragments not identifiable from their osteomorphological studies by proteomics analysis

The ancient preserved molecules offer the opportunity to gain a better knowledge on the biological past. In recent years, bones proteomics has become an attractive method to study the animal biological origin, extinct species and species evolution as an alternative to DNA analysis which is limited by DNA amplification present in ancient samples and its contamination. However, the development of a proteomic workflow remains a challenge. The analysis of fossils must consume a low quantity of material to avoid damaging the samples. Another difficulty is the absence of genomic data for most of the extinct species. In this study, a proteomic methodology was applied to mammalian bones of 130,000 years old from the earlier Upper Pleistocene site of Scladina Cave (Belgium). Starting from 5 milligram samples, our results show a large majority of detected peptides matching collagen I alpha 1 and alpha 2 proteins with a sequence coverage up to 60%. Using sequence homology with modern sequences, a biological classification was successfully achieved and the associated taxonomic ranks to each bone were identified consistently with the information gained from osteomorphological studies and palaeoenvironmental and palaeodietary data. Among the taxa identified are the Felidae family, Bovinae subfamily, Elephantidae family and the Ursus genus. Amino acid substitutions on the collagens were identified providing new information on extinct species sequences and also helping in taxonomy-based clustering. Considering samples with no osteomorphological information, such as two bone retouchers, proteomics successfully identified the bovidae and ursidae families providing new information to the paleontologists on these objects. Combining osteomorphology studies and amino acid variations identified by proteomics, one retoucher was identified to be potentially from the Ursus spelaeus species.

paleontology↗