RESUMEN
Human glial progenitor cells (hGPCs) exhibit diminished expansion competence with age, as well as after recurrent demyelination. Using RNA-sequencing to compare the gene expression of fetal and adult hGPCs, we identify age-related changes in transcription consistent with the repression of genes enabling mitotic expansion, concurrent with the onset of aging-associated transcriptional programs. Adult hGPCs develop a repressive transcription factor network centered on MYC, and regulated by ZNF274, MAX, IKZF3, and E2F6. Individual over-expression of these factors in iPSC-derived hGPCs lead to a loss of proliferative gene expression and an induction of mitotic senescence, replicating the transcriptional changes incurred during glial aging. miRNA profiling identifies the appearance of an adult-selective miRNA signature, imposing further constraints on the expansion competence of aged GPCs. hGPC aging is thus associated with acquisition of a MYC-repressive environment, suggesting that suppression of these repressors of glial expansion may permit the rejuvenation of aged hGPCs.
Asunto(s)
Envejecimiento , MicroARNs , Neuroglía , Factores de Transcripción , Humanos , Neuroglía/metabolismo , Neuroglía/citología , Envejecimiento/genética , Envejecimiento/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , MicroARNs/genética , MicroARNs/metabolismo , Senescencia Celular/genética , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre/metabolismo , Células Madre/citología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Redes Reguladoras de Genes , Proliferación Celular/genética , Regulación del Desarrollo de la Expresión Génica , Perfilación de la Expresión GénicaRESUMEN
The invasive species Lonicera maackii (Amur Honeysuckle) is an increasing problem sweeping from the eastern United States toward the west, impacting normal forest development and animal survival across multiple taxa. Little is known about the genomics of this species, although a related invasive, Lonicera japonica, has been sequenced. Understanding the genomic foundation of the Lonicera maackii species could help us understand the biochemistry and life history that are the underpinnings of invasive success, as well as potential vulnerabilities and strengths which could guide research and development to control its spread. Here we present a draft, but high-quality, short-read whole-genome sequence, assembly, and annotation of Lonicera maackii, demonstrating that inexpensive and rapid short-read technologies can be successfully used in invasive species research. Despite being a short-read assembly, the genome length (7.93 × 108) and completeness (estimated as 90.2-92.1% by BUSCO and Merqury) are close to the previously published chromosome-level sequencing of L. japonica. No bias, by means of a Gene Ontology analysis, was identified among missing BUSCOs. A duplication of the 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase gene in both Lonicera species is identified, and the potential impact on controlling these invasive species is discussed. Future prospects for a diversity analysis of invasive species is also discussed.