Ask about this productRelated genes to: HNF1A Blocking Peptide
- Gene:
- HNF1A NIH gene
- Name:
- HNF1 homeobox A
- Previous symbol:
- MODY3, TCF1
- Synonyms:
- HNF1, LFB1
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 1990-02-12
- Date modifiied:
- 2019-04-23
Related products to: HNF1A Blocking Peptide
Related articles to: HNF1A Blocking Peptide
- HNF1A-MODY, the most common monogenic diabetes, exhibits progressive β cell dysfunction, but existing mouse models fail to recapitulate human disease progression, limiting understanding of pathogenic mechanisms. We developed mice with heterozygous deletion of the Hnf1a transactivation domain (Hnf1a+/Δe4-10) to model human HNF1A haploinsufficiency, conducted cross-sectional metabolic characterization, and validated our findings in HNF1A-deficient human islets. Unlike previous models, Hnf1a+/Δe4-10 mice successfully recapitulated temporal HNF1A-MODY progression. Male mice developed sequential pathophysiology: early insulin resistance in young adults (7 weeks), followed by testosterone deficiency and fasting hyperglycemia in adult mice (10 weeks). Glucose intolerance emerged in middle-aged mice (30 weeks), progressing to multi-organ dysfunction in aged mice (44-70 weeks), characterized by elevated hepatic gluconeogenesis, impaired renal glucose handling, and hepatic steatosis/fibrosis. This dual pathophysiology involving β cell dysfunction and peripheral insulin resistance was associated with dysregulated hormone secretion from both α and β cells in aged mice (40-70 weeks). Human islet studies with HNF1A knockdown confirmed translational relevance, demonstrating reduced SGLT2 protein expression and inappropriate glucagon and insulin secretion. This work established a physiologically relevant HNF1A-MODY model, identified early insulin resistance as a key mechanism triggering hormonal dysfunction, and revealed HNF1A's role in multi-organ pathophysiology beyond traditional β cell dysfunction. - Source: PubMed
Publication date: 2026/05/08
Louvet IsalineAcosta-Montalvo AnaSaponaro ChiaraMoreno-Lopez MariaDouffi SanaEl Karchaoui AbdelkrimPasquetti GianniThevenet JulienDelalleau NathalieGmyr ValeryGiacobini PaoloEspiard StéphanieKerr-Conte JuliePattou FrançoisListon AdrianBonner Caroline - Psoriasis frequently relapses after treatment withdrawal, consistent with persistent epigenetic programs in lesional immune cells. Lysine acetylation is a reversible regulatory layer linking chromatin accessibility, transcription factor activity, and immune-cell effector programs; yet, its cell-type-resolved landscape and clinical stratification value in psoriasis remain incompletely defined. We integrated four bulk transcriptome cohorts of psoriatic and healthy skin (746 psoriasis, 515 controls) with two public skin scRNA-seq datasets. A diagnostic acetylation-regulator signature was derived from 33 curated acetylation regulators, and acetylation endotypes were defined by unsupervised clustering. The cell-type-specific expression was mapped at the single-cell resolution. Key regulators were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an imiquimod-induced psoriasis-like mouse model, and further verified in an independent dataset (GSE136757). Motif enrichment and drug-target mining were used to prioritize transcriptional regulators and candidate epigenetic therapeutics. Sixteen acetylation regulators were differentially expressed in bulk skin, with histone deacetylase (HDAC1) showing the strongest upregulation and lysine acetyltransferase (KAT2A) the strongest downregulation. A 13-gene acetylation signature discriminated psoriasis from controls (area under the curve, AUC 0.886) and separated lesional samples into two acetylation endotypes with divergent pathway states (hypoxia-glycolysis versus oxidative-stress-dominated programs). Single-cell mapping demonstrated immune-restricted acetylation modules, including CREB binding protein (CREBBP)-enriched neutrophils, histone deacetylase 1 (HDAC1)-high cluster of differentiation (CD)8 T cells, and lysine acetyltransferase 6A (KAT6A)/lymphoid enhancer binding factor (LEF1)-enriched CD4 and regulatory T cell (Treg) subsets, coincident with interleukin (IL)-17-related inflammatory programs. In mice, qRT-PCR confirmed the coordinated dysregulation of hub genes and highlighted Hnf1a and Kat6a as reproducible candidates. External validation using the GSE136757 dataset further supports their robust diagnostic performance. Motif analysis nominated interferon regulatory factor (IRF4), YY transcription factor (YY2), and zinc finger protein (ZNF404) as putative transcriptional mediators downstream of acetylation programs, and drug-target mining prioritized epigenetic compounds with subtype-relevant potential, including histone deacetylase (HDAC) inhibitors (e.g., entinostat) and the p300/CREB binding protein (CBP) inhibitor A485. This integrative atlas links acetylation regulators to specific immune compartments, defines acetylation endotypes associated with distinct inflammatory programs, and provides a rationale for stratified epigenetic target selection in psoriasis. - Source: PubMed
Publication date: 2026/04/01
Xie MengjiMa XiaoxuanZhang YingKuai LeLuo YingSong JiankunDing XiaojieRu YiLuo YueFei XiaoyaHong SeokgyeongDeng GuoshuSu YonghuaWang RuipingLi BinXiang YanweiLi MiaoZhou Mi - In this issue of , Unger and colleagues (doi:10.1101/gad.353153.125) combined human pluripotent stem cell-derived in vitro models with targeted in vivo mouse models to reveal multiple developmental defects triggered by mutations causing maturity-onset diabetes of the young. This work paints the picture of a disorder that starts well before diabetes manifests, highlighting its complexity arising from the diverse roles of HNF1A across distinct cell types, each potentially differentially impacted by different mutations. - Source: PubMed
Publication date: 2026/04/22
Warin JulieGrapin-Botton Anne - Oligogenic inheritance in maturity-onset diabetes of the young (MODY) remains poorly characterized, and the contribution of multiple candidate variants to disease pathogenesis is incompletely understood. - Source: PubMed
Publication date: 2026/04/23
Honda MakieHonda RyoNomura Teiko KomoriNishikado YuichiTakahashi YoshihiroHosomichi KazuyoshiTsunekawa ShinYabe DaisukeHorikawa Yukio - Adoptive T cell therapies typically rely on ex vivo CD3/CD28 stimulation, which promotes effector differentiation and limits the persistence of transferred cells. Stem cell-like memory T cells (Tscm), with their capacity for self-renewal and multipotency, represent an ideal therapeutic subset but remain difficult to generate at scale. Here, we present a CD3-independent strategy using artificial antigen-presenting cells expressing a membrane-bound CD28 superagonist (αCD28-aAPCs) to expand CD8 T cells with Tscm-like features. In naïve CD8 T cells, αCD28-aAPC stimulation initiates a distinct transcriptional and epigenetic program, marked by high TCF1 expression, metabolic fitness, and resistance to exhaustion-key hallmarks of the Tscm phenotype. Mechanistically, this approach circumvents canonical CD3/TCR signaling and notably avoids induction of IRF4, a key transcription factor that drives BLIMP1 upregulation, TCF1 downregulation, and glycolytic commitment during effector differentiation. Instead, sustained CD28 signaling alone reprograms T cells toward a Tscm-like state. Upon subsequent antigen encounter and CD3 engagement, these αCD28-aAPC-expanded T cells mount robust effector responses while retaining superior persistence and antitumor activity in preclinical models. Our findings reveal an underappreciated role of CD28 signaling in guiding Tscm-like fate through IRF4 suppression and establish a platform for generating durable and functionally potent T cell therapies. - Source: PubMed
Publication date: 2026/04/21
Ihara FumieOhashi YotaZheng Evey Y FFukao SaoriRodrigo RowenaNoamani BabakBoukhaled Giselle MWang Ben XHan Dong-HoonWei XinyuBurt Brian DSaso KayokoMatsunaga YukikoLy DalamKagoya YukiButler Marcus OMak Tak WSaibil Samuel DHirano Naoto