Integrative molecular roadmap for direct conversion of fibroblasts into myocytes and myogenic progenitor cells

Transient MyoD overexpression in concert with small molecule treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multiomics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Using transcriptomics, proteomics, and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories that govern the two processes. Notably, only iMPC reprogramming is characterized by gradual up-regulation of muscle stem cell markers, unique signaling pathways, and chromatin remodelers in conjunction with exclusive chromatin opening in core myogenic promoters. In addition, we determine that the Notch pathway is indispensable for iMPC formation and self-renewal and further use the Notch ligand Dll1 to homogeneously propagate iMPCs. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs for capturing myogenesis ex vivo

TRIM5-mediated retrovirus restriction is modulated by type I interferon.

Since the identification in 2004 of the interferon-stimulated gene (ISG) tripartite motif-containing protein 5 α (TRIM5α) from rhesus macaques as a restriction factor preventing HIV-1 infection in these monkeys, the antiretroviral activity of several primate TRIM5α orthologs against HIV-1 has been described, establishing the model that TRIM5α inhibits retroviral infection in a species-specific manner, preventing host cell infection by retroviruses from different species through fragmentation of incoming viral capsids and the activation of innate immune pathways. However, the long held dogma that retroviruses have evolved to evade the TRIM5α ortholog present in species to which they are endemic has recently changed by the identification of human TRIM5α as a major determinant in the Type 1 IFNinduced suppression of HIV-1 replication, presumably contributing to the immune control of HIV-1 in infected humans. Given that IFN levels are elevated during natural retrovirus infection and that IFN treatment enables human TRIM5α restriction of HIV-1, we evaluated the IFN-induced restriction of distinct retroviruses in presence of TRIM5α orthologues from different primate species. To this end, we ectopically expressed different TRIM5α orthologues in human U87 cells where endogenous TRIM5α and MX2 expression had been ablated using CRISPR–Cas9 genome editing, and then challenged with a wide range of GFP-encoding retrovirus-based vectors in the presence or absence of IFN. This approach reveals that IFN treatment changes the patterns of TRIM5α-mediated retrovirus restriction, suggesting that the role of TRIM5α in retrovirus infection should be re-examined under conditions that more closely mimic those encountered during natural virus infection.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Extraordinary centromeres: differences in the meiotic chromosomes of two rock lizards species Darevskia portschinskii and Darevskia raddei

According to the synthesis of 30 years of multidisciplinary studies, parthenogenetic species of rock lizards of genus Darevskia were formed as a result of different combination patterns of interspecific hybridization of the four bisexual parental species: Darevskia raddei, D. mixta, D. valentini, and D. portschinskii. In particular, D. portschinskii and D. raddei are considered as the parental species for the parthenogenetic species D. rostombekowi. Here for the first time, we present the result of comparative immunocytochemical study of primary spermatocyte nuclei spreads from the leptotene to diplotene stages of meiotic prophase I in two species: D. portschinskii and D. raddei. We observed similar chromosome lengths for both synaptonemal complex (SC) karyotypes as well as a similar number of crossing over sites. However, unexpected differences in the number and distribution of anti-centromere antibody (ACA) foci were detected in the SC structure of bivalents of the two species. In all examined D. portschinskii spermatocyte nuclei, one immunostained centromere focus was detected per SC bivalent. In contrast, in almost every studied D. raddei nuclei we identified three to nine SCs with additional immunostained ACA foci per SC bivalent. Thus, the obtained results allow us to identify species-specific karyotype features, previously not been detected using conventional mitotic chromosome analysis. Presumably the additional centromere foci are result of epigenetic chromatin modifications. We assume that this characteristic of the D. raddei karyotype could represent useful marker for the future studies of parthenogenetic species hybrid karyotypes related to D. raddei

Integrative molecular roadmap for direct conversion of fibroblasts into myocytes and myogenic progenitor cells

Transient MyoD overexpression in concert with small molecules treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multi-omics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Utilizing transcriptomics, proteomics and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories which govern the two processes. Notably, iMPC reprogramming is characterized by gradual upregulation of stem and progenitor cell markers, unique signaling pathways, chromatin remodelers and cell cycle regulators which manifest via rewiring of the chromatin in core myogenic promoters. Furthermore, we determine that only iMPC reprogramming is mediated by Notch pathway activation, which is indispensable for iMPC formation and self-renewal. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs in capturing myogenesis ex vivo

Reticulate Evolution of the Rock Lizards: Meiotic Chromosome Dynamics and Spermatogenesis in Diploid and Triploid Males of the Genus Darevskia

Knowing whether triploid hybrids resulting from natural hybridization of parthenogenetic and bisexual species are fertile is crucial for understanding the mechanisms of reticulate evolution in rock lizards. Here, using males of the bisexual diploid rock lizard species Darevskia raddei nairensis and Darevskia valentini and a triploid hybrid male Darevskia unisexualis × Darevskia valentini, we performed karyotyping and comparative immunocytochemistry of chromosome synapsis and investigated the distribution of RAD51 and MLH1 foci in spread spermatocyte nuclei in meiotic prophase I. Three chromosome sets were found to occur in cell nuclei in the D. unisexualis × D. valentini hybrid, two originating from a parthenogenetic D. unisexualis female and one from the D. valentini male. Despite this distorted chromosome synapsis and incomplete double-strand breaks repair in meiotic prophase I, the number of mismatch repair foci in the triploid hybrid was enough to pass through both meiotic divisions. The defects in synapsis and repair did not arrest meiosis or spermatogenesis. Numerous abnormal mature spermatids were observed in the testes of the studied hybrid

Integrative molecular roadmap for direct conversion of fibroblasts into myocytes and myogenic progenitor cells

Transient MyoD overexpression in concert with small molecule treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multiomics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Using transcriptomics, proteomics, and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories that govern the two processes. Notably, only iMPC reprogramming is characterized by gradual up-regulation of muscle stem cell markers, unique signaling pathways, and chromatin remodelers in conjunction with exclusive chromatin opening in core myogenic promoters. In addition, we determine that the Notch pathway is indispensable for iMPC formation and self-renewal and further use the Notch ligand Dll1 to homogeneously propagate iMPCs. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs for capturing myogenesis ex vivo.ISSN:2375-254

Effects of an External Magnetic Field on the Interband and Intraband Optical Properties of an Asymmetric Biconvex Lens-Shaped Quantum Dot

The theoretical investigation of interband and intraband transitions in an asymmetric biconvex lens-shaped quantum dot are considered in the presence of an external magnetic field. The selection rules for intraband transitions are obtained. The behaviors of linear and nonlinear absorption and photoluminescence spectra are observed for different temperatures and magnetic field strengths. The second and third harmonic generation coefficients as a function of the photon energy are examined both in the absence and presence of an external magnetic field

Realization of the Kohn’s Theorem in Ge/Si Quantum Dots with Hole Gas: Theory and Experiment

This article discusses specific quantum transitions in a few-particle hole gas, localized in a strongly oblate lens-shaped quantum dot. Based on the adiabatic method, the possibility of realizing the generalized Kohn theorem in such a system is shown. The criteria for the implementation of this theorem in a lens-shaped quantum dot, fulfilled in the experiment, is presented. An analytical expression is obtained for the frequencies of resonant absorption of far-infrared radiation by a gas of heavy holes, which depends on the geometric parameters of the quantum dot. The results of experiments on far-infrared absorption in the arrays of p-doped Ge/Si quantum dots grown by molecular beam epitaxy (MBE) with gradually increasing average number of holes in dot are presented. Experimental results show that the Coulomb interaction between the holes does not affect the resonant frequency of the transitions. A good agreement between the theoretical and experimental results is shown