Tempo-iMG™: Architectural Strategies

May 10, 2023 | Citation Alerts

Tempo-iMG™ was cited in cell.com in a study that investigated HIV-1 integration in the unexplored microglia reservoir that gives rise to continued HIV replication in infected cells. Scientists used Tempo-iMG™ human iPSC-derived microglia to determine that CTCF, an architectural chromosomal protein, contributes to the viral integration and latency and is found proximally to topologically associated domains (TAD) within H3K36me3-enriched areas. The authors of the article cited Tempo-iMG as an accurate, patient-relevant human model that can be used to represent microglial HIV-infections in the human central nervous system.

Citation Summary

In this citation, researchers investigated HIV-1 integration sites (ISs) to better understand the preferential areas of genomic access during HIV infection, and they wanted to understand signature genomic motifs and proteins that play critical regulatory roles. 

HIV-1 targets transcriptionally active genes and is dependent on the interaction of two viral proteins, integrase and capsid. Within genomic regions of targeted high transcription, HIV-1 targets super-enhancers (SEs) and speckle-associated domains (SPADs). SEs are proximal to HIV-1 insertion patterns in the transcriptionally active A1 subcompartment, which contains specifically segregated chromosomes based on interactions with gene-active and gene-inactive regions. Within the A and B compartments, TADs are folded by cohesin-dependent loop extrusions that, when enriched by CTCF, form TAD boundaries which are conserved among different cell types.  Patient-derived samples suggest the existence of replication-competent proviruses, years after antiretroviral therapy (ART). ART flare ups, combined with microglial activation, and neuroinflammation contribute to long-term destructive disorders such as HIV-associated neurological disorders (HANDs). 

To investigate this relationship, scientists researched HIV-1 ISs, transcriptional output, and chromatin signatures of HIV-1 genomic regions utilizing Tempo-iMG™ which provided researchers with a patient-relevant microglia that displayed comparable insertion and transcription profiles as human microglial cells.  In this investigation, scientists demonstrated that the depletion of CTCF, a major architectural protein that insulates TADs, reduces HIV-1 integration levels and alters ISs. Based on this discovery, the authors proposed further exploration of the 3D genome and its functional implications to better understand HIV-1 infection. 

Tempo-iMG citation alert. HIV study.

Tempo Bioscience Product Relevance

Tempo-iMG™ are human-derived iPSC-derived microglia. Authors cited this product for its physiological relevance in modeling HIV-infection in microglia. Past studies of HIV-infected microglia have been hindered by limited tissue availability from both HIV positive patients and healthy donors. This prevented researchers from being able to effectively evaluate human microglial function and genomic consequences of an HIV infection.