RFX6 is needed for the development and maintenance of the β-cell phenotype

Taleb, Nadine; Polychronakos, Constantin

doi:10.4161/isl.3.5.15944

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…When ranked by their correlation with delta fate, we identified Map2k4, Msi1 and Nefl as novel candidate regulators. Msi1 is regulated by Rfx4 54 , which is a paralog of Rfx6 that is structurally related to Rfx3 55 , both of which are involved in endocrine differentiation 50,56–60 .…”

Section: Resultsmentioning

confidence: 99%

CellRank for directed single-cell fate mapping

Theis

Lange

Bergen

et al. 2020

Preprint

113

202

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Computational trajectory inference enables the reconstruction of cell-state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for mapping the fate of single cells in diverse scenarios, including perturbations such as regeneration or disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, derived from ratios of spliced to unspliced reads. CellRank takes into account both the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in RNA velocity vectors. On data from pancreas development, we show that it automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. CellRank also predicts a novel dedifferentiation trajectory during regeneration after lung injury, which we follow up experimentally by confirming the existence of previously unknown intermediate cell states.

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Section: Resultsmentioning

confidence: 99%

CellRank for directed single-cell fate mapping

Theis

Lange

Bergen

et al. 2020

Preprint

113

202

View full text Add to dashboard Cite

show abstract

“…By quantitative real-time PCR, pancreatic RFX6 expression is limited to adult human islet cells, and autosomal recessive mutations at this locus result in neonatal diabetes, with absence of insulin + , glucagon + , and somatostatin + cells [50,51]. Similarly, Rfx6 -deficient mice exhibit impaired formation of all endocrine cell types except for pancreatic polypeptide [50].…”

Section: Endocrine Cell Specificationmentioning

confidence: 99%

“…Although Rfx6 is expressed more broadly and earlier than Ngn3 during mouse development, Rfx6 expression is not detected in Ngn3 −/− mice. Interestingly, human NGN3 mutations result in milder diabetes cases than RFX6 mutations [51]. Thus, RFX6 could act either upstream or downstream of NGN3 in coordinating the production of a subset of islet cell types [50,51].…”

Section: Endocrine Cell Specificationmentioning

confidence: 99%

Revealing transcription factors during human pancreatic β cell development

Conrad

Stein

Hunter³

2014

Trends in Endocrinology & Metabolism

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Developing cell-based diabetes therapies requires examining transcriptional mechanisms underlying human β cell development. However, increased knowledge is hampered by low availability of fetal pancreatic tissue and gene targeting strategies. Rodent models have elucidated transcription factor roles during islet organogenesis and maturation, but differences between mouse and human islets have been identified. The past 5 years have seen strides toward generating human β cell lines, the examination of human transcription factor expression, and studies utilizing induced pluripotent stem cells (iPS cells) and human embryonic stem (hES) cells to generate β-like cells. Nevertheless, much remains to be resolved. We present current knowledge of developing human β cell transcription factor expression, as compared to rodents. We also discuss recent studies employing transcription factor or epigenetic modulation to generate β cells.

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“…There are studies showing the involvement of this gene in the differentiation of islet cells and regulation of transcription factors involved in beta cell function thereby affecting insulin production [4]. Mitchell-riley syndrome is considered to be an association of a particular phenotype of Martinez-frias syndrome, and it was suggested that both represent an RFX6 malformation complex [5,6]. The expression of RFX6 gene starts early in embryonic development throughout the anterior endoderm and later on is confined to the gut and pancreas endocrine cells [1,7].…”

Section: Discussionmentioning

confidence: 99%

A Case of Neonatal Diabetes and Multiple Congenital Anomalies: Variant of Mitchell-riley/Martinez-frias Syndrome

Alqanea

2024

J Clin Ped Res.

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Neonatal diabetes along with congenital anomalies like duodenal atresia, tracheoesophageal fistula, intra uterine growth retardation, extrahepatic biliary obstruction and hypoplasia of pancreas is a very rare occurrence with evidence linking it to RFX6 gene mutation. The presence in newborn babies necessitates a detailed genetic evaluation and multidisciplinary management. Here, we present a preterm baby with persistent neonatal hyperglycemia and gastrointestinal anomalies similar to cases associated with Mitchel-riley/Martinez-frias syndrome.

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RFX6 is needed for the development and maintenance of the β-cell phenotype

Abstract: Extensive research is needed to specify this role and explore its significance in the efforts to treat diabetes with medications, or more importantly, through β-cell replacement.

Cited by 12 publications

References 18 publications

CellRank for directed single-cell fate mapping

CellRank for directed single-cell fate mapping

Revealing transcription factors during human pancreatic β cell development

A Case of Neonatal Diabetes and Multiple Congenital Anomalies: Variant of Mitchell-riley/Martinez-frias Syndrome

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