Liyuan Jiang

Mettl3-mediated m 6 A regulates spermatogonial differentiation and meiosis initiation

METTL3 catalyzes the formation of N6-methyl-adenosine (m6A) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m6A profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of Mettl3-mediated m6A modification in spermatogenesis and reproduction in mammals.

Thermal stability of Ir-Mn∕Co-Fe-B∕Al-O∕Co-Fe-B tunnel junctions

The thermal stability of magnetic tunnel junctions with structures of Ta(5)∕Cu(30)∕Ta(5)∕Ni79Fe21(5)∕Ir22Mn78(12)∕Co62Fe20B18(4)∕Al(0.8)-oxide∕Co62Fe20B18(4)∕Cu(30)∕Ta(5) (thicknesses unit in nanometers) has been investigated. The tunnel magnetoresistance (TMR) shows a large increase up to 54.4% after annealing at 265u2009°C due to the improved characteristic properties of the barrier and the interface between the barrier and the ferromagnetic electrodes. The TMR was observed to decrease drastically above the annealing temperature of 310u2009°C accompanied by a notable increase of junction resistance and coercivity of the free layer. The amorphous Co62Fe20B18 layers seem to behave as a barrier of diffusion, preventing the migration of Mn or Cu atoms into the interface between the barrier and the ferromagnetic layers. This may cause the drastic decrease of TMR due to the deterioration of the barrier and its interface with Co62Fe20B18 layers. The observed crystallization in the amorphous Co62Fe20B18 layers is consi...

Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis

Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis

Effect of Magnetic Field Annealing Upon Co-Rich Nanowires

The magnetic field (MF) annealing of dc electrodeposited ferromagnetic nanowire arrays of compositions Co94Fe06 , Co91Fe07B2 was done in the direction of their easy axis of magnetization (in plane) at 2650 C under 800 Oe applied magnetic field for 2 h. An induced magnetic anisotropy (MA) and a large increase in saturation magnetization (Ms) were manifested by the changes in hysteresis loops of the nanowire samples before and after the annealing process. The structural changes were investigated using X-ray diffraction and transmission electron microscopy (TEM). The shape of nanowires, the predicted natural texture with c-axis in the plane of membrane (because of high concentration of cobalt) and diffusional pair ordering of unlike atoms along the direction of external applied field were thought to be the causes of induced MA. The reannealing of samples in absence of MF at 400degC and 600degC produced no significant changes in hysteresis loops instead of removing the MA but with evolution of crystalline phase in both the samples. Therefore, the shape of nanowire was concluded to play the major role in persistence of induced MA in nanowire samples after high temperature annealing

METTL3-mediated m6A modification is required for cerebellar development

N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here, we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout (cKO) mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion–induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.

Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

Meiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis. Highlights Identification of a female meiosis-specific cyclin in mouse Cyclin B3 is required for metaphase-anaphase transition in oocyte meiosis I Cyclin B3 is not essential for oocyte maturation and sister chromosome segregation Cyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1