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Biology subjects

Lei, W.-L.

Publications and source records attributed to Lei, W.-L..

2 recordsLinked to original sources

SRSF2 is required for mRNA splicing and spermatogenesis

RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.

developmental biology↗

Enhancing NeuroD1 Expression to Convert Lineage-Traced Astrocytes into Neurons

Regenerating functional new neurons in adult mammalian brains has been proven a difficult task for decades. Recent advancement in direct glia-to-neuron conversion in vivo opens a new field for neural regeneration and repair. However, this emerging new field is facing serious challenges from misuse of viral vectors to misinterpretation of conversion data. Here, we employ a variety of AAV vectors with different promoters and enhancers to demonstrate that astrocytes can be converted into neurons in a NeuroD1 dose-dependent manner in both wildtype (WT) and transgenic mice. Notably, astrocytes in WT mice were relatively easy to convert with higher conversion efficiency, whereas lineage-traced astrocytes in Aldh1l1-CreERT2 mice showed high resistance to reprogramming but were still converted into neurons after enhancing NeuroD1 expression with CMV enhancer. Furthermore, under two-photon microscope, we observed direct astrocyte-to-neuron conversion within 3 weeks of serial live imaging in the mouse cortex. We also demonstrated that high titre AAV reaching 1013 GC/ml caused severe neuronal leakage using a variety of AAV GFAP::GFP vectors, highlighting the necessity to inject low titre AAV into healthy brains to avoid artifactual results. Together, our studies suggest that lineage-traced astrocytes can be converted into neurons but require stronger conversion force such as enhanced NeuroD1 expression. Failure to recognize the difference between WT astrocytes and lineage-traced astrocytes in terms of conversion barrier will lead to misinterpretation of data.

neuroscience↗