Conserved functional antagonism of CELF 1 and MBNL proteins controls stem cell-specific alternative splicing in planarians

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS in animal stem cell regulation across metazoans

Conservation research in times of COVID-19 - the rescue of the northern white rhino

COVID-19 has changed the world at unprecedented pace. The measures imposed by governments across the globe for containing the pandemic have severely affected all facets of economy and society, including scientific progress. Сonservation research has not been exempt from these negative effects, which we here summarize for the BioRescue project, aiming at saving the northern white rhinoceros (Ceratotherium simum cottoni), an important Central African keystone species, of which only two female individuals are left. The development of advanced assisted reproduction and stem-cell technologies to achieve this goal involves experts across five continents. Maintaining international collaborations under conditions of national shut-down and travel restrictions poses major challenges. The associated ethical implications and consequences are particularly troublesome when it comes to research directed at protecting biological diversity – all the more in the light of increasing evidence that biodiversity and intact ecological habitats might limit the spread of novel pathogens

Naïve-like pluripotency to pave the way for saving the northern white rhinoceros from extinction

The northern white rhinoceros (NWR) is probably the earth's most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naïve-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naïve culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naïve-like NWR iPSCs displayed increased expression of naïve and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naïve-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells.Toxicolog