NKX6-1

Last update 08 May 2025

Basic Info

Synonyms

Homeobox protein NK-6 homolog A, Homeobox protein Nkx-6.1, NK6 homeobox 1

+ [3]

Introduction

Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Involved in the development of insulin-producing beta cells in the islets of Langerhans at the secondary transition (By similarity). Together with NKX2-2 and IRX3 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals (By similarity).

100 Clinical Results associated with NKX6-1

100 Translational Medicine associated with NKX6-1

0 Patents (Medical) associated with NKX6-1

135

Literatures (Medical) associated with NKX6-1

01 Apr 2025·Molecular and Cellular Endocrinology

Expression of genes involved in thyroid hormone action in human induced pluripotent stem cells during differentiation to insulin-producing cells: Effects of iopanoic acid on differentiation

Article

Author: Shiojima, Ichiro ; Hattori, Fumiyuki ; Osafune, Kenji ; Toyoda, Nagaoki ; Kimura, Azuma ; Maruoka, Azusa ; Hitomi, Hirofumi

AIMSType 3 iodothyronine deiodinase (Dio3) converts triiodothyronine (T3) to diiodothyronine, thereby reducing intracellular T3 levels. In this study, we investigated the potential roles of Dio3 in the differentiation of human pancreatic β cells, using β cells derived from human induced pluripotent stem cells (hiPSCs).MAIN METHODShiPSCs were differentiated to β cells in a stepwise manner over 29 days. The differentiation medium was supplemented with B27, which contains T3 but not T4, instead of serum. The T3 levels in the differentiated cells were determined based on the amount of T3 supplied to the medium and the activity of Dio3 within the cells. Iopanoic acid (IOP) was used as the Dio3 inhibitor.KEY FINDINGSDio3 expression is substantially altered during differentiation. IOP treatment reduced Dio3 activity on day 4 and increased T3 levels in the medium on day 29. To investigate the involvement of Dio3 during differentiation, we used IOP, in which cells differentiated in the presence of IOP (+IOP) were compared to those differentiated without IOP (-IOP). On day 29, the proportion of β cells expressing C-peptide, NKX6 homeobox 1, and both markers was considerably higher in the presence than in the absence of IOP. Furthermore, on day 29, the insulin content of differentiated + IOP cells was considerably higher than that of differentiated -IOP cells.CONCLUSIONSAn increase in intracellular T3 content promoted via the inhibition of Dio3 activity by IOP from day 0-29 enhances the differentiation of hiPSCs to β cells.

01 Dec 2024·Diabetologia

Deletion of RFX6 impairs iPSC-derived islet organoid development and survival, with no impact on PDX1+/NKX6.1+ progenitors

Article

Author: Hayat, Sikander ; Memon, Bushra ; Ijaz, Sadaf ; Abdelalim, Essam M ; Aldous, Noura ; Elsayed, Ahmed K

AbstractAims/hypothesisHomozygous mutations in RFX6 lead to neonatal diabetes accompanied by a hypoplastic pancreas, whereas heterozygous mutations cause MODY. Recent studies have also shown RFX6 variants to be linked with type 2 diabetes. Despite RFX6’s known function in islet development, its specific role in diabetes pathogenesis remains unclear. Here, we aimed to understand the mechanisms underlying the impairment of pancreatic islet development and subsequent hypoplasia due to loss-of-function mutations in RFX6.MethodsWe examined regulatory factor X6 (RFX6) expression during human embryonic stem cell (hESC) differentiation into pancreatic islets and re-analysed a single-cell RNA-seq dataset to identify RFX6-specific cell populations during islet development. Furthermore, induced pluripotent stem cell (iPSC) lines lacking RFX6 were generated using CRISPR/Cas9. Various approaches were then employed to explore the consequences of RFX6 loss across different developmental stages. Subsequently, we evaluated transcriptional changes resulting from RFX6 loss through RNA-seq of pancreatic progenitors (PPs) and endocrine progenitors (EPs).ResultsRFX6 expression was detected in PDX1+ cells in the hESC-derived posterior foregut (PF). However, in the PPs, RFX6 did not co-localise with pancreatic and duodenal homeobox 1 (PDX1) or NK homeobox 1 (NKX6.1) but instead co-localised with neurogenin 3, NK2 homeobox 2 and islet hormones in the EPs and islets. Single-cell analysis revealed high RFX6 expression levels in endocrine clusters across various hESC-derived pancreatic differentiation stages. Upon differentiating iPSCs lacking RFX6 into pancreatic islets, a significant decrease in PDX1 expression at the PF stage was observed, although this did not affect PPs co-expressing PDX1 and NKX6.1. RNA-seq analysis showed the downregulation of essential genes involved in pancreatic endocrine differentiation, insulin secretion and ion transport due to RFX6 deficiency. Furthermore, RFX6 deficiency resulted in the formation of smaller islet organoids due to increased cellular apoptosis, linked to reduced catalase expression, implying a protective role for RFX6. Overexpression of RFX6 reversed defective phenotypes in RFX6-knockout PPs, EPs and islets.Conclusions/interpretationThese findings suggest that pancreatic hypoplasia and reduced islet cell formation associated with RFX6 mutations are not due to alterations in PDX1+/NKX6.1+ PPs but instead result from cellular apoptosis and downregulation of pancreatic endocrine genes.Data availabilityRNA-seq datasets have been deposited in the Zenodo repository with accession link (DOI: https://doi.org/10.5281/zenodo.10656891).Graphical Abstract

03 Sep 2024·Technology and Health Care

Identifying the regulatory network of microRNAs and mRNAs to clarify molecular mechanisms in stroke by bioinformatics analysis

Article

Author: Cen, Gengyu ; Xia, Yumei ; Liang, Zhijian

BACKGROUND: Stroke is one of the leading causes of disability and mortality worldwide. OBJECTIVE: To identify the regulatory network of microRNAs (miRNAs) and mRNAs to clarify molecular mechanisms in stroke. METHODS: Four miRNA datasets and two mRNA datasets of stroke were downloaded from the GEO database. R-Studio was utilized to analyze differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in the blood of stroke and control patients. FunRich software was utilized to conduct GO and biological pathway analysis on DEmiRNAs, and to search for transcription factors (TFs) of DEmiRNAs. Subsequently, we used miRDB, miRTarBase, and TargetScan to identify DEmiRNAs target genes and intersected with DEmRNAs to find common target genes. The miRNA-mRNA regulatory network of common target genes was constructed by using the Cytoscape. The biological and functional roles of target genes in the regulatory network were predicted using GO and KEGG pathway analyses. RESULTS: 464 DEmiRNAs and 329 DEmRNAs were screened. The top ten TFs (SP1, SP4, EGR1, TCF3, NKX6-1, ZFP161, RREB1, MEF2A, NFIC, POU2F1) were visualized. 16747 target genes of DEmiRNAs were predicted. Target genes were intersected with DEmRNAs, 107 common target genes and 162 DEmiRNAs regulating these common genes were obtained, and then a regulatory network was constructed. Target genes of the regulatory network were primarily enriched in VEGF signaling pathway, lipid and atherosclerosis, T cell receptor signaling pathway. CONCLUSION: This study found that VEGF signaling pathway, lipid and atherosclerosis, T cell receptor signaling pathway are implicated in the biological process of stroke by constructing the regulatory network of miRNAs-mRNAs, which may have guide significance for the pathogenesis and treatment of stroke.

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NKX6-1

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