Transplantation of Pro-Oligodendroblasts, Preconditioned by LPS-Stimulated Microglia, Promotes Recovery After Acute Contusive Spinal Cord Injury

Spinal cord injury (SCI) is a significant clinical challenge, and to date no effective treatment is available. Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair. However, the poor posttransplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as donor cells. Here we report the generation of an OL lineage population [i.e., pro-oligodendroblasts (proOLs)] that is relatively more mature than OPCs for transplantation after SCI. We found that proOLs responded to lipopolysaccharide (LPS)-stimulated microglia conditioned medium (L+M) by preserving toll-like receptor 4 (TLR4) expression, improving cell viability, and enhancing the expression of a myelinating OL marker myelin basic protein (MBP), compared to other OL lineage cells exposed to either LPS-stimulated (L+M) or nonstimulated microglia conditioned medium (L−M). When L+M-stimulated proOLs were intrathecally delivered through a lumbar puncture after a T10 thoracic contusive SCI, they promoted behavioral recovery, as assessed by the Basso‐Beattie‐Bresnahan (BBB) locomotor rating scale, stride length, and slips on the grid tests. Histologically, transplantation of L+M proOLs caused a considerable increase in intralesional axon numbers and myelination, and less accumulation of invading macrophages when compared with the vehicle control or OPC transplantation. Thus, transplantation of proOLs, preconditioned by L+M, may offer a better therapeutic potential for SCI than OPCs since the former may have initiated the differentiation process toward OLs prior to transplantation

Signaling pathways in hair aging

Hair follicle (HF) homeostasis is regulated by various signaling pathways. Disruption of such homeostasis leads to HF disorders, such as alopecia, pigment loss, and hair aging, which is causing severe health problems and aesthetic concerns. Among these disorders, hair aging is characterized by hair graying, hair loss, hair follicle miniaturization (HFM), and structural changes to the hair shaft. Hair aging occurs under physiological conditions, while premature hair aging is often associated with certain pathological conditions. Numerous investigations have been made to determine the mechanisms and explore treatments to prevent hair aging. The most well-known hypotheses about hair aging include oxidative stress, hormonal disorders, inflammation, as well as DNA damage and repair defects. Ultimately, these factors pose threats to HF cells, especially stem cells such as hair follicle stem cells, melanocyte stem cells, and mesenchymal stem cells, which hamper hair regeneration and pigmentation. Here, we summarize previous studies investigating the above mechanisms and the existing therapeutic methods for hair aging. We also provide insights into hair aging research and discuss the limitations and outlook

Data Mining and Validation of AMPK Pathway as a Novel Candidate Role Affecting Intramuscular Fat Content in Pigs

Intramuscular fat (IMF) is an important economic trait for pork quality and a complex quantitative trait regulated by multiple genes. The objective of this work was to investigate the novel transcriptional effects of a multigene pathway on IMF deposition in the longissimus dorsi (LD) muscles of pigs. Potential signaling pathways were screened by mining data from three gene expression profiles in the Gene Expression Omnibus (GEO) database. We designed quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) arrays for the candidate signaling pathways to verify the results in the LD muscles of two pig breeds with different IMF contents (Large White and Min). Western blot analysis was used to detect the expression levels of several candidate proteins. Our results showed that the AMPK signaling pathway was screened via bioinformatics analysis. Ten key hub genes of this signaling pathway (AMPK, ADIPOR1, ADIPOR2, LKB1, CAMKKβ, CPT1A, CPT1B, PGC-1α, CD36, and ACC1) were differentially expressed between the Large White and Min pigs. Western blot analysis further confirmed that LKB1/CaMKK2-AMPK-ACC1-CPT1A axis dominates the activity of AMPK signaling pathway. Statistical analyses revealed that AMPK signaling pathway activity clearly varied among the two pig breeds. Based on these results, we concluded that the activation of the AMPK signaling pathway plays a positive role in reducing IMF deposition in pigs

A two-level model for the role of complex and young genes in the formation of organism complexity and new insights into the relationship between evolution and development

Abstract Background How genome complexity affects organismal phenotypic complexity is a fundamental question in evolutionary developmental biology. Previous studies proposed various contributing factors of genome complexity and tried to find the connection between genomic complexity and organism complexity. However, a general model to answer this question is lacking. Here, we introduce a ‘two-level’ model for the realization of genome complexity at phenotypic level. Results Five representative species across Protostomia and Deuterostomia were involved in this study. The intrinsic gene properties contributing to genome complexity were classified into two generalized groups: the complexity and age degree of both protein-coding and noncoding genes. We found that young genes tend to be simpler; however, the mid-age genes, rather than the oldest genes, show the highest proportion of high complexity. Complex genes tend to be utilized preferentially in each stage of embryonic development, with maximum representation during the late stage of organogenesis. This trend is mainly attributed to mid-age complex genes. In contrast, young genes tend to be expressed in specific spatiotemporal states. An obvious correlation between the time point of the change in over- and under-representation and the order of gene age was observed, which supports the funnel-like model of the conservation pattern of development. In addition, we found some probable causes for the seemingly contradictory ‘funnel-like’ or ‘hourglass’ model. Conclusions These results indicate that complex and young genes contribute to organismal complexity at two different levels: Complex genes contribute to the complexity of individual proteomes in certain states, whereas young genes contribute to the diversity of proteomes in different spatiotemporal states. This conclusion is valid across the five species investigated, indicating it is a conserved model across Protostomia and Deuterostomia. The results in this study also support ‘funnel-like model’ from a new viewpoint and explain why there are different evo–devo relation models

The Possible Role of Complete Loss of Myostatin in Limiting Excessive Proliferation of Muscle Cells (C2C12) via Activation of MicroRNAs

Myostatin (MSTN) is a member of the TGF-β superfamily that negatively regulates skeletal muscle growth and differentiation. However, the mechanism by which complete MSTN deletion limits excessive proliferation of muscle cells remains unclear. In this study, we knocked out MSTN in mouse myoblast lines using a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system and sequenced the mRNA and miRNA transcriptomes. The results show that complete loss of MSTN upregulates seven miRNAs targeting an interaction network composed of 28 downregulated genes, including TGFB1, FOS and RB1. These genes are closely associated with tumorigenesis and cell proliferation. Our study suggests that complete loss of MSTN may limit excessive cell proliferation via activation of miRNAs. These data will contribute to the treatment of rhabdomyosarcoma (RMS)

Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes

Although the “missing protein” is a temporary concept in C-HPP, the biological information for their “missing” could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 proteins (with no transcript evidence). These missing-protein-encoding genes distribute unevenly among different chromosomes, chromosomal regions, or gene clusters. In the view of evolutionary features, PE3/4 genes tend to be young, spreading at the nonhomology chromosomal regions and evolving at higher rates. Interestingly, there is a higher proportion of singletons in PE3/4 genes than the proportion of singletons in all genes (background) and OTCSGs (organ, tissue, cell type-specific genes). More importantly, most of the paralogous PE3/4 genes belong to the newly duplicated members of the paralogous gene groups, which mainly contribute to special biological functions, such as “smell perception”. These functions are heavily restricted into specific type of cells, tissues, or specific developmental stages, acting as the new functional requirements that facilitated the emergence of the missing-protein-encoding genes during evolution. In addition, the criteria for the extremely special physical–chemical proteins were first set up based on the properties of PE2 proteins, and the evolutionary characteristics of those proteins were explored. Overall, the evolutionary analyses of missing-protein-encoding genes are expected to be highly instructive for proteomics and functional studies in the future