ArticleStem cells (Dayton, Ohio)2015
A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- T3 enhances neuronal activity in an induced pluripotent stem cell derived model of early human brain development.European thyroid journal · 2026Article
- Convergent thyroid-ATPase interactions regulate collective behavior in Danionella.Cell reports · 2026Article
- Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)-Induced Polycystic Ovary Syndrome via Liver-Ovary Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lead induces cell-autonomous proliferation and metabolic reprogramming of hepatocytes.Cell death & disease · 2025Article
- TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility.Scientific reports · 2025Article
- Thyroid hormone receptor beta (THRβ1) is the major regulator of T3 action in human iPSC-derived hepatocytes.Molecular metabolism · 2024Article
- Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.Arthritis research & therapy · 2024Article
- Review
- Postpartum scarcity-adversity inflicts sex-specific cerebellar adaptations and reward behaviors in adolescence.Pharmacology, biochemistry, and behavior · 2023Article
- Loss of Krüppel-like factor 9 deregulates both physiological gene expression and development.Scientific reports · 2023Article
- Potential use of TG68 - A novel thyromimetic - for the treatment of non-alcoholic fatty liver (NAFLD)-associated hepatocarcinogenesis.Frontiers in oncology · 2023Article
- The thyroid hormone enhances mouse embryonic fibroblasts reprogramming to pluripotent stem cells: role of the nuclear receptor corepressor 1.Frontiers in endocrinology · 2023Article
- Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2023Article
- Dioxin Disrupts Thyroid Hormone and Glucocorticoid Induction of klf9, a Master Regulator of Frog Metamorphosis.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Article
- Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells.Stem cell research & therapy · 2022Article
- Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes.Biomedicines · 2022Article
- Article
- TransSynW: A single-cell RNA-sequencing based web application to guide cell conversion experiments.Stem cells translational medicine · 2021Article
- Glucocorticoid-Responsive Transcription Factor Krüppel-Like Factor 9 RegulatesFrontiers in cell and developmental biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Biological processes require close cooperation of multiple transcription factors that integrate different signals. Thyroid hormone receptors (TRs) induce Krüppel-like factor 9 (KLF9) to regulate neurogenesis. Here, we show that triiodothyronine (T3) also works through TR to induce KLF9 in HepG2 liver cells, mouse liver, and mouse and human primary hepatocytes and sought to understand TR/KLF9 network function in the hepatocyte lineage and stem cells. Knockdown experiments reveal that KLF9 regulates hundreds of HepG2 target genes and modulates T3 response. Together, T3 and KLF9 target genes influence pathways implicated in stem cell self-renewal and differentiation, including Notch signaling, and we verify that T3 and KLF9 cooperate to regulate key Notch pathway genes and work independently to regulate others. T3 also induces KLF9 in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSC) and this effect persists during differentiation to definitive endoderm and hiPSC-derived hepatocytes. Microarray analysis reveals that T3 regulates hundreds of hESC and hiPSC target genes that cluster into many of the same pathways implicated in TR and KLF9 regulation in HepG2 cells. KLF9 knockdown confirms that TR and KLF9 cooperate to regulate Notch pathway genes in hESC and hiPSC, albeit in a partly cell-specific manner. Broader analysis of T3 responsive hESC/hiPSC genes suggests that TRs regulate multiple early steps in ESC differentiation. We propose that TRs cooperate with KLF9 to regulate hepatocyte proliferation and differentiation and early stages of organogenesis and that TRs exert widespread and important influences on ESC biology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.