HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo DOI Creative Commons

Ting-Ya Chang,

David J. Waxman

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 24, 2024

STARR-seq and other massively-parallel reporter assays are widely used to discover functional enhancers in transfected cell models, which can be confounded by plasmid vector-induced type-I interferon immune responses lack the multicellular environment endogenous chromatin state of complex mammalian tissues. We describe HDI-STARR-seq, combines library delivery liver, hydrodynamic tail vein injection (HDI), with RNA transcriptional initiation driven a minimal Albumin promoter, we show is essential for mouse liver enhancer activity assayed 7 days after HDI. Importantly, little or no innate were observed. Comparisons HDI-STARR-seq between male female livers from males treated an activating ligand transcription factor (TF) CAR (Nr1i3) identified many condition-dependent linked condition-specific gene expression. Further, thousands active using high complexity comprised ~ 50,000 genomic regions released DNase-I digestion nuclei. When compared stringently inactive sequences, sequences highly enriched open histone marks (H3K27ac, H3K4me1, H3K4me3), significantly closer start sites, depleted repressive (H3K27me3, H3K9me3) transcribed region (H3K36me3). offers substantial improvements over current methodologies large scale, profiling enhancers, including tissue vivo, adapted characterize activities variety species tissues selecting suitable tissue- species-specific promoter sequences.

Language: Английский

Progress of pediatric liver transplantation: In Japan and beyond DOI Creative Commons
Mureo Kasahara, Seisuke Sakamoto

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Organ transplantation, particularly pediatric liver transplantation (LT), has transformed medical practice over the past six decades, providing life-saving interventions for children with end-stage disease. This review demonstrated historical milestones of organ emphasizing Japan’s contributions, mainly through National Center Child Health and Development. While early efforts in 1950s 1960s faced significant challenges, breakthroughs preservation methods, immunosuppressive therapies, surgical techniques, innovations such as living donor LT Asia have greatly improved success rates. landscape is distinct, primarily due to its reliance on LT, shaped by cultural religious influences that traditionally restricted deceased donation. manuscript discusses pioneering role expanding indications include rare conditions inherited metabolic disorders hepatoblastoma. It highlights recent hyper-reduced lateral segment grafts, machine perfusion, minimally invasive surgery further outcomes. International collaboration facilitated sharing expertise, advancing live worldwide. Despite these achievements, challenges remain, light declining birth rate, which threatens sustainability transplant services. emphasizes need centralized facilities, greater awareness brain-dead donation, continued advances ensure remains a viable, option future generations.

Language: Английский

Citations

0

HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo DOI Creative Commons

Ting-Ya Chang,

David J. Waxman

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 24, 2024

STARR-seq and other massively-parallel reporter assays are widely used to discover functional enhancers in transfected cell models, which can be confounded by plasmid vector-induced type-I interferon immune responses lack the multicellular environment endogenous chromatin state of complex mammalian tissues. We describe HDI-STARR-seq, combines library delivery liver, hydrodynamic tail vein injection (HDI), with RNA transcriptional initiation driven a minimal Albumin promoter, we show is essential for mouse liver enhancer activity assayed 7 days after HDI. Importantly, little or no innate were observed. Comparisons HDI-STARR-seq between male female livers from males treated an activating ligand transcription factor (TF) CAR (Nr1i3) identified many condition-dependent linked condition-specific gene expression. Further, thousands active using high complexity comprised ~ 50,000 genomic regions released DNase-I digestion nuclei. When compared stringently inactive sequences, sequences highly enriched open histone marks (H3K27ac, H3K4me1, H3K4me3), significantly closer start sites, depleted repressive (H3K27me3, H3K9me3) transcribed region (H3K36me3). offers substantial improvements over current methodologies large scale, profiling enhancers, including tissue vivo, adapted characterize activities variety species tissues selecting suitable tissue- species-specific promoter sequences.

Language: Английский

Citations

0