Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation <em>in vivo</em>

Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome reorganisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGF beta). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation

EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization

CGL was funded by the Consejería de Salud y Familias, Junta de Andalucía (RH-0139-2020) and SG-P is funded by Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533). JAM is supported by RTI2018.101309B-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and by the Chair “Doctors Galera-Requena in cancer stem cell research”. PCS is funded by Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00) and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20). The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005), the Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants.Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial–mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.Junta de Andalucía (RH-0139-2020)Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533)MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” RTI2018.101309B-C22Chair “Doctors Galera-Requena in cancer stem cell research”Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00)FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20)Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005)Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681)University of Granada (A-BIO-6-UGR20

25 years of African trypanosome research:From description to molecular dissection and new drug discovery

The Molecular Parasitology conference was first held at the Marine Biological laboratory, Woods Hole, USA 25 years ago. Since that first meeting, the conference has evolved and expanded but has remained the showcase for the latest research developments in molecular parasitology. In this perspective, I reflect on the scientific discoveries focussed on African trypanosomes (Trypanosoma brucei spp.) that have occurred since the inaugural MPM meeting and discuss the current and future status of research on these parasites

The molecular basis of cell memory in mammals: The epigenetic cycle

Cell memory refers to the capacity of cells to maintain their gene expression program once the initiating environmental signal has ceased. This exceptional feature is key during the formation of mammalian organisms, and it is believed to be in part mediated by epigenetic factors that can endorse cells with the landmarks required to maintain transcriptional programs upon cell duplication. Here, we review current literature analyzing the molecular basis of epigenetic memory in mammals, with a focus on the mechanisms by which transcriptionally repressive chromatin modifications such as methylation of DNA and histone H3 are propagated through mitotic cell divisions. The emerging picture suggests that cellular memory is supported by an epigenetic cycle in which reversible activities carried out by epigenetic regulators in coordination with cell cycle transition create a multiphasic system that can accommodate both maintenance of cell identity and cell differentiation in proliferating stem cell populations.Grant (EUR2021-122005) funded by MCIN/AEI/10.13039/501100011033Spanish Ministry of Science and Innovation (PID2022-137060NB-I00 and PID2019-108108-100)Instituto de Salud Carlos III (IHRC22/00007)Andalusian regional government (PC-0246-2017, PIER-0211-2019, and PY20_00681)University of Granada (A-BIO-6-UGR20

Cinemática de cães da raça pastor alemão hígidos em displasia coxofemoral

O trabalho teve por objetivos avaliar padrões cinemáticos dos membros torácicos e pélvicos em cães hígidos da raça Pastor Alemão, ao trote em esteira, e compará-los com cães displásicos da mesma raça sem sinais clínicos de claudicação, para determinar a viabilidade do método como contribuinte diagnóstico. Foi utilizado um total de 20 cães, divididos em dois grupos equitativos, a saber: Grupo 1 – cães hígidos, seis machos e quatro fêmeas, com peso médio de 27,3 a 46 kg (média = 35,76 kg, DP= 5,87) e idade entre 2 e 7 anos (média de 3,55 anos); Grupo 2 – cães com displasia coxofemoral, cinco machos e cinco fêmeas, com peso entre 29 e 41,6 (média = 35,33 kg; DP= 4,36) e idade variando de 1 a 5 anos (média de 3,35 anos). Os dados cinemáticos foram coletados com o emprego de três câmeras e analisados por um programa de análise de movimento. Foram registrados os valores angulares e a velocidade angular das articulações do ombro, cotovelo, do carpo, coxofemoral, joelho e do tarso. Em ambos os Grupos não foram observadas diferenças na média entre os membros pélvicos ou entre os membros torácicos em todas as variáveis analisadas. Não ocorreu diferença de valores angulares entre os Grupos. Para a velocidade angular foram observadas diferenças na velocidade angular máxima da articulação coxofemoral (displásico>hígido) e do carpo (hígido>displásico). Foi possível concluir que cães displásicos sem sinais clínicos de claudicação podem apresentar ao trote alterações cinemáticas tanto nos membros pélvicos como torácicosThe aim of this study was to establish kinematic patterns in clinically normal German shepherd dogs and to compare with dogs of the same breed with hip dysplasia with no clinical signs of lameness to determine the importance as auxiliary diagnosis method. Twenty intact German shepherd trotting on a treadmill at a constant speed were used. Ten clinically healthy dogs, 6 males and 4 females, weighing 27.3-46 kg (mean 35.76 kg ± 5.87 SD), and aged from 2 to 7 years (mean 3.55 years) (G1), and 10 dogs with hip dysplasia, weighing 29-41.6 kg (mean 35.33 kg ± 4.36 SD), and aged from 1 to 5 years (mean 3.35 years) (G2). Kinematic data were collected by use of a 3-camera system. Data were analyzed by use of a motion-analysis program. Flexion and extension joint angles, angular velocity and angular acceleration were determined for the shoulder, elbow, carpal, hip, stifle, and tarsal joints. Within each group, the differences between the right and left limbs in all kinematic variables were not significant. No differences were observed in joint angles (maximum, minimum, displacement) between Groups. Significant differences were observed in the maximum angular velocity of the hip joint (dysplastic>healthy) and carpal joint (healthy>dysplastic). In conclusion, dysplastic dogs with no signs of lameness trotting on a treadmill may present joint kinematic alterations in the hind limbs as well as forelimbsConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Energetic Implications of Morphological Changes between Fish Larval and Juvenile Stages Using Geometric Morphometrics of Body Shape

The fish body shape is a key factor that influences multiple traits such as swimming, foraging, mating, migrations, and predator avoidance. The present study describes the body morphological changes and the growth trajectories during the transformation from 24 to 54 days post-hatching in the golden grey mullet, Chelon auratus, using geometric morphometric analysis (GMA). The results revealed a decrease in morphological variability (i.e., morphological disparity) with the somatic growth. The main changes affected head size, elongation, and widening of the body. Given that this variability could affect the metabolism, some individuals with different morphologies and in different ontogenetic developmental stages were selected to estimate their potential respiration rate using the Electron Transport System (ETS) analysis. Differences were detected depending on the developmental stage, and being significantly smaller after 54 days post-hatching. Finally, a multivariate linear regression indicated that the specific ETS activity was partially related to the fish length and body shape. Thus, our findings emphasized the relevance of larval morphological variability for understanding the physiological processes that occur during the development