Rafael D. Acemel

A small polymerase ribozyme that can synthesize itself and its complementary strand The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller?

Excited to share our latest work in @science.org on a new small polymerase.
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Preocupación por las expectativas creadas por Barbacid sobre el cáncer de páncreas: “El anuncio se ha salido de madre” Varios centros de investigación están recibiendo una avalancha de peticiones tras un anuncio que, según muchos especialistas, ha sido mal comunicado: ni Barbacid ha encontrado la cura del cáncer de pá...

Para el turno de tarde: Preocupación por las expectativas creadas por Barbacid sobre el cáncer de páncreas: “El anuncio se ha salido de madre” www.eldiario.es/1_c5dac3?utm...

Thanks!!! 😊

And finally, we have It out! Do not miss It, If you are into early eye development, GRNs, and eye malformations. Thanks to Javier Macho and the rest of the authors for a terrific job.

🚨 1/ Preprint Alert!

Sex determination outcome is conserved across vertebrates (i.e. generating 2 compatible sexes) ♀️♂️

But are the cell types and gene programs behind them conserved too? 🧬

Spoiler: not really 👀

Find out in our new preprint ⬇️

www.biorxiv.org/content/10.6...

In depth analysis and more nuanced discussions can be found in the paper. Thanks again to all the authors. We are eager to receive feedback!

Based on this, we propose that supporting cells from Pax2-positive cells is an ancestral feature of Archelosauria, and those cells might be more prone to become steroidogenic. In contrast, in mammals supporting cells derive mostly from cells from the coelomic epithelium.

In fact, #BorisTezak immunos on T. scripta confirmed the coexpression of Pax2 and Sox9.

We performed PAGA trajectory analysis, which are consistent with the idea that supporting cells in turtles (granulosa and Sertoli) derive mostly from Pax2-positive mesenchymal cells.

Indeed, supporting cells in mice and chickens are thought to come from different progenitors. In mouse they mostly derive from coelomic epithelium cells, while in chicken mainly from a Pax2-positive mesenchymal population.

But if non-mammalian supporting cells are steroidogenic, then are they really homologous to mammalian supporting cells? And where do they come from?

Our data supports a model in which fetal Leydig cells (interstitially derived) could be a mammalian innovation. In fact, in mammals, androgens are dispensable for sex determination and only required to fully masculinize the embryo. Outside mammals, androgens are produced by supporting lineage cells!

Again, #BorisTezak performed some nice immunos validating the colocalization of the steroidogenic gene Cyp11a1 with supporting cells that are also Sox9 positive.

We checked in turtles, and bingo! Androgen producing enzymes such as Cyp11a1 are produced by cells of the supporting lineage in T. scripta. Then, exclusively in ovaries, as in chicken, the aromatase Cyp19a1 converts androgens into estrogens in granulosa cells.

While fetal Leydig cells and theca cells have been identified in chicken, these steroidogenic populations derive from supporting cells, not interstitial cells!

However, we could not find interstitial cells expressing steroidogenic enzymes in T. scripta. This was puzzling: androgens and estrogens are critical for sex determination in turtles. However we think there is a catch!

But this was not the only surprise. Given the conservation of main gonadal lineages, we expected to find the equivalent of fetal Leydig cells in mammals: a population mainly derived from interstitial cells and in charge of producing androgens.

To explore this relationship closer #BorisTezak did some beautiful immunos showing the transient coexpression of Twist1 and Sox9 followed by the downregulation of the latter in female gonads of T. scripta.

Twist1 is the first transcription factor differentially expressed in female cells. It is not expressed there either in mouse or chicken and has never been implicated in sex determination before! However, Twist1 has been shown to antagonize Sox9, a pro-testicular gene, but in mouse chondrogenesis 👀.

Thus, to identify new factors involved in sex determination in turtles we looked for genes differentially expressed in supporting cell progenitors at either MPT and FPT. We did not find many, but one of them caught our attention: Twist1.

After data integration we found that all main gonadal lineages are conserved: germinal, interstitial and supporting cells. Supporting cells are often first to read sex determining inputs, differentiating into either Sertoli cells in males or granulosa cells in females and guiding other cell types.

Insights into Gonadal Sex Differentiation Provided by Single-Cell Transcriptomics in the Chicken Embryo Gonadal cell-lineage specification during embryogenesis has long been thought to be similar among vertebrates. In this chicken study, Estermann et al. show that this is not the case, finding major dif...

Importantly, we could rely on previous single-cell data in chicken from the #Smith lab (www.cell.com/cell-reports...) and in mouse from the #Nef lab (www.science.org/doi/10.1126/...) to aid in the annotation and perform evolutionary comparisons!

To uncover cell types and genetic programs involved in sex determination in T. scripta we performed single-cell RNA-seq experiments at either MPT or FPT in three different timepoints: before (Yntema Stg.15), during (Stg. 18) and after (Stg. 23) sex determination.

To answer this question we studied the sex determination process of the turtle Trachemys scripta. In this species, embryos incubated at 26ºC (the male producing temperature, MPT) develop as males while embryos incubated at 31ºC (FPT) develop as females.

From a more Evo Devo perspective, we were fascinated on how cell types and sex determining networks may evolve to integrate genetic (like mammals and birds) or environmental (turtles) sex-determining inputs.

Environmental Warming and Feminization of One of the Largest Sea Turtle Populations in the World Increasing incubation temperature impacts species with temperature-dependent sex determination such as green sea turtles. Jensen et al. combined genetic and endocrine techniques to show that an import...

But why should we care? Well, species with temperature‑dependent sex determination (TSD) are more vulnerable to global warming. For instance, sex ratios in the green sea turtle (Chelonia mydas) are increasingly skewed toward females raising conservation concerns.
www.cell.com/current-biol...

But first, many thanks to all authors! @dariloops.bsky.social, #BorisTezak, #BlancheCapel, #VickyChung, #AliciaHurtado, @ceriweber.bsky.social, #ScarlettAlbertson.

New preprint!! 🚨 Did you know that many vertebrate species determine sex based on environmental conditions rather than chromosomes? Some turtles, like Trachemys scripta, rely on temperature. We learned more about how this happen molecularly.👇
www.biorxiv.org/content/10.6...

Back in BCN after an great week in Valencia, 1st meeting of #EvoDevOmics network with @mirimiam.bsky.social @anariesgo.bsky.social @evodevogenomeub.bsky.social @patrialvarezcam.bsky.social @jpascualanaya.bsky.social @phylobrain.bsky.social @fany-real.bsky.social @imaeso.bsky.social & Nuria Flames

Thanks a lot to all the authors and @jrmarmor.bsky.social for putting everything together!