Improved Tol2-mediated enhancer trap identifies weakly expressed genes during liver and β cell development and regeneration in zebrafish

In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

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Prolonged Prepregnant Maternal High-Fat Feeding Reduces Fetal and Neonatal Blood Glucose Concentrations by Enhancing Fetal β-cell Development in C57BL/6 Mice

Diabetes ◽

10.2337/db18-1308 ◽

2019 ◽

pp. db181308 ◽

Cited By ~ 2

Author(s):

Liping Qiao ◽

Jean-Sebastien Wattez ◽

Lauren Lim ◽

Paul J. Rozance ◽

William W. Hay ◽

...

Keyword(s):

Blood Glucose ◽

Cell Development ◽

High Fat ◽

Β Cell ◽

Neonatal Blood ◽

Blood Glucose Concentrations ◽

Fat Feeding

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NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01977-0 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Idil I. Aigha ◽

Essam M. Abdelalim

Keyword(s):

Transcription Factor ◽

Cell Function ◽

Disease Modeling ◽

Critical Role ◽

Cell Mass ◽

Cell Development ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Β Cell Function

Abstract Understanding the biology underlying the mechanisms and pathways regulating pancreatic β cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing β cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive to β cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1+/NKX6.1+), warrants their future commitment to monohormonal β cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1+/NKX6.1−) results in an undesirable generation of non-functional polyhormonal β cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a means to increase β cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.

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Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00619.2011 ◽

2012 ◽

Vol 302 (11) ◽

pp. E1431-E1439 ◽

Cited By ~ 29

Author(s):

Adriana Rodríguez-Trejo ◽

María Guadalupe Ortiz-López ◽

Elena Zambrano ◽

María de los Ángeles Granados-Silvestre ◽

Carmen Méndez ◽

...

Keyword(s):

Aggregate Size ◽

Later Life ◽

Developmental Programming ◽

Cell Development ◽

Cell Fraction ◽

Mrna Levels ◽

Β Cell ◽

Low Protein ◽

Protein Diets ◽

In Pregnancy

Maternal low-protein diets (LP) impair pancreatic β-cell development, resulting in later-life failure and susceptibility to type 2 diabetes (T2D). We hypothesized that intrauterine and/or postnatal developmental programming seen in this situation involve altered β-cell structure and relative time course of expression of genes critical to β-cell differentiation and growth. Pregnant Wistar rats were fed either control (C) 20% or restricted (R) 6% protein diets during pregnancy (1st letter) and/or lactation (2nd letter) in four groups: CC, RR, RC, and CR. At postnatal days 7 and 21, we measured male offspring β-cell fraction, mass, proliferation, aggregate number, and size as well as mRNA level for 13 key genes regulating β-cell development and function in isolated islets. Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. We conclude that LP in pregnancy sets the trajectory of postnatal β-cell growth and differentiation, whereas LP in lactation has smaller effects. We propose that LP promotes differentiation through upregulation of transcription factors that stimulate differentiation at the expense of proliferation. This results in a decreased β-cell reserve, which can contribute to later-life predisposition to T2D.

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