Stroke remains the number one cause of morbidity in the United States. Within weeks to months after an ischemic event, there is a resolution of inflammation and evidence of neurogenesis; however, years following a stroke, there is evidence of chronic inflammation in the central nervous system, possibly by the persistence of an autoimmune response to brain antigens as a result of ischemia. The mechanisms underlying the involvement of macrophage and microglial activation after stroke are widely acknowledged as having a role in ischemic stroke pathology; thus, modulating inflammation and neurological recovery is a hopeful strategy for treating the long-term outcomes after ischemic injury. Current treatments fail to provide neuroprotective or neurorestorative benefits after stroke; therefore, to ameliorate brain injury-induced deficits, therapies must alter both the initial response to injury and the subsequent inflammatory process. This review will address differences in macrophage and microglia nomenclature and summarize recent work in elucidating the mechanisms of macrophage and microglial participation in antigen presentation, neuroprotection, angiogenesis, neurogenesis, synaptic remodeling, and immune modulating strategies for treating the long-term outcomes after ischemic injury.

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases. miRNA-p63 interactions are also critical regulators in the context of cancer metastasis. This review aims to elaborate on the diverse roles of p63, focusing on disease, development, and the mechanisms controlling genome organization and function.

A persistent barrier to the cure and treatment of neurological diseases is the limited ability of the central and peripheral nervous systems to undergo neuroregeneration and repair. Recent efforts have turned to regeneration of various cell types through cellular reprogramming of native cells as a promising therapy to replenish lost or diminished cell populations in various neurological diseases. This review provides an in-depth analysis of the current viral vectors, genes of interest, and target cellular populations that have been studied, as well as the challenges and future directions of these novel therapies. Furthermore, the mechanisms by which cellular reprogramming could be optimized as treatment in neurological diseases and a review of the most recent cellular reprogramming in vitro and in vivo studies will also be discussed.

Currently, there is a significant shortage of transplantable organs for patients in need. Interspecies chimerism and blastocyst complementation are alternatives for generating transplantable human organs in host animals such as pigs to meet this shortage. While successful interspecies chimerism and organ generation have been observed between evolutionarily close species such as rat and mouse, barriers still exist for more distant species pairs such as human–mouse, marmoset–mouse, human–pig, and others. One of the proposed barriers to chimerism is the difference in developmental stages between the donor cells and the host embryo at the time the cells are introduced into the host embryo. Hence, there is a logical effort to stage-match the donor cells with the host embryos for enhancing interspecies chimerism. In this study, we used an in silico approach to simultaneously stage-match the early developing embryos of four species, including human, marmoset, mouse, and pig based on transcriptome similarities. We used an unsupervised clustering algorithm to simultaneously stage-match all four species as well as Spearman’s correlation analyses to stage-match pairs of donor–host species. From our stage-matching analyses, we found that the four stages that best matched with each other are the human blastocyst (E6/E7), the gastrulating mouse embryo (E6–E6.75), the marmoset late inner cell mass, and the pig late blastocyst. We further demonstrated that human pluripotent stem cells best matched with the mouse post-implantation stages. We also performed ontology analysis of the genes upregulated and commonly expressed between donor–host species pairs at their best matched stages. The stage-matching results predicted by this study will inform in vivo and in vitro interspecies chimerism and blastocyst complementation studies and can be used to match donor cells with host embryos between multiple species pairs to enhance chimerism for organogenesis.

A growing need for organs and novel cell-based therapies has provided a niche for approaches like interspecies chimeras. To generate organs from one donor species in another host species requires techniques such as blastocyst complementation and gene editing to successfully create an embryo that has cells from both the donor and the host. However, the task of developing highly efficacious and competent interspecies chimeras is met by many challenges. These interspecies chimeric barriers impede the formation of chimeras, often leading to lower levels of chimeric competency. The barriers that need to be addressed include the evolutionary distance between species, stage-matching, temporal and spatial synchronization of developmental timing, interspecies cell competition and the survival of pluripotent stem cells and embryos, compatibility of ligand–receptor signaling between species, and the ethical concerns of forming such models. By overcoming the interspecies chimera barriers and creating highly competent chimeras, the technology of organ and cellular generation can be honed and refined to develop fully functioning exogenic organs, tissues, and cells for transplantation.

Analysis of a cell’s replication timing (RT) provides insight into how genes replicate, early or late, during the S-phase of the cell cycle. RT is cell-type specific, inheritable, and has been correlated to gene expression in normal and diseased states. However, most studies have been limited to somatic cells. Very little is known about RT control in early mouse embryos, and how it correlates with the start of transcription during zygote gene activation (ZGA), at the 2-cell stage. In this study, we develop an in-house single-cell multiomics approach to simultaneously analyze RT and gene expression in individual cells of the mouse 1-cell, 2-cell, and 4-cell embryos. We detect that RT is established at the 1-cell stage prior to ZGA. Surprisingly, we observe that the coordinated RT and gene expression control is different in early totipotent embryos, compared to previously published studies in somatic cells. Late replicating regions correlate with higher gene expression and open chromatin in the early developing embryos. Lastly, we perform an integrated pseudo time trajectory analysis combining RT and gene expression information per cell.