scholarly journals Analysis of the expression of PIWI-interacting RNAs during cardiac differentiation of human pluripotent stem cells

2019 ◽  
Author(s):  
Alejandro La Greca ◽  
María Agustina Scarafía ◽  
María Clara Hernández Cañás ◽  
Nelba Pérez ◽  
Sheila Castañeda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Development ◽  
Germ Line ◽  
Cardiac Cells ◽  
Cardiac Differentiation ◽  
Fine Tuning ◽  
Protein Coding ◽  
Sense Strand ◽  
And Function

SummaryPIWI-interacting RNAs (piRNAs) are a class of non-coding RNAs initially thought to be restricted almost exclusively to germ line cells. In recent years, accumulating evidence has demonstrated that piRNAs are actually expressed in somatic cells like pluripotent, neural, cardiac and even cancer cells. However, controversy still remains around the existence and function of somatic piRNAs. Using small RNA-seq samples from H9 pluripotent stem cells differentiated to mesoderm progenitors and cardiomyocytes we identified the expression of 447 piRNAs, of which 241 were detected in pluripotency, 218 in mesoderm and 171 in cardiac cells. The majority of them originated from the sense strand of protein coding and lncRNAs genes in all stages of differentiation, though no evidences for secondary piRNAs (ping-pong loop) were found. Genes hosting piRNAs in cardiac samples were related to critical biological processes in the heart, like contraction and cardiac muscle development. Our results indicate that somatic piRNAs might have a role in fine-tuning the expression of genes involved in the differentiation of pluripotent cells to cardiomyocytes.

scholarly journals LncRNA HBL1 is required for genome-wide PRC2 occupancy and function in cardiogenesis from human pluripotent stem cells

Development ◽  
2021 ◽  
Author(s):  
Juli Liu ◽  
Sheng Liu ◽  
Lei Han ◽  
Yi Sheng ◽  
Yucheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Transcription ◽  
Pluripotent Stem Cells ◽  
Cardiac Development ◽  
Chromatin Modification ◽  
Human Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Genome Wide ◽  
And Function

Polycomb Repressive Complex 2 (PRC2) deposits H3K27me3 on chromatin to silence transcription. PRC2 broadly interacts with RNAs. Currently, the role of RNA- PRC2 interaction in human cardiogenesis remains elusive. Here, we found human-specific Heart Brake LncRNA 1 (HBL1) interacted with two PRC2 subunits, JARID2 and EED, in human pluripotent stem cells (hPSCs). Loss-of-JARID2, EED or HBL1 significantly enhanced cardiac differentiation from hPSCs. HBL1 depletion disrupted genome-wide PRC2 occupancy and H3K27me3 chromatin modification on essential cardiogenic genes, and broadly enhanced cardiogenic gene transcription in undifferentiated hPSCs and later-on differentiation. Additionally, ChIP-seq revealed reduced EED-occupancy on 62 overlapped cardiogenic genes in HBL1−/- and JARID2−/- hPSCs, indicating the epigenetic state of cardiogenic genes was determined by HBL1 and JARID2 at pluripotency stage. Furthermore, after cardiac development occurred, the cytosolic and nuclear fractions of HBL1 could crosstalk via a conserved “microRNA-1-JARID2” axis to modulate cardiogenic gene transcription. Overall, our findings delineate the indispensable role of HBL1 in guiding PRC2 function during early human cardiogenesis, and expand the mechanistic scope of lncRNA(s) that cytosolic and nuclear portions of HBL1 could coordinate to orchestrate human cardiogenesis.

scholarly journals Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

2020 ◽  
Vol 21 (2) ◽  
pp. 507
Author(s):  
Alessandra Maria Lodrini ◽  
Lucio Barile ◽  
Marcella Rocchetti ◽  
Claudia Altomare
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Cardiac Cells ◽  
Cardiac Differentiation ◽  
Human Ipscs ◽  
Wide Range ◽  
Induced Pluripotent

Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized the complex scientific field of disease modelling and personalized therapy. Cardiac differentiation of human iPSCs into cardiomyocytes (hiPSC-CMs) has been used in a wide range of healthy and disease models by deriving CMs from different somatic cells. Unfortunately, hiPSC-CMs have to be improved because existing protocols are not completely able to obtain mature CMs recapitulating physiological properties of human adult cardiac cells. Therefore, improvements and advances able to standardize differentiation conditions are needed. Lately, evidences of an epigenetic memory retained by the somatic cells used for deriving hiPSC-CMs has led to evaluation of different somatic sources in order to obtain more mature hiPSC-derived CMs.

scholarly journals Transposable Element-Gene Splicing Modulates the Transcriptional Landscape of Human Pluripotent Stem Cells

2020 ◽  
Author(s):  
Isaac A. Babarinde ◽  
Gang Ma ◽  
Yuhao Li ◽  
Boping Deng ◽  
Zhiwei Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Genome Stability ◽  
Human Pluripotent Stem Cells ◽  
Endogenous Retroviruses ◽  
Rna Seq ◽  
Protein Coding ◽  
Gene Splicing ◽  
Mammalian Genomes ◽  
And Function

AbstractTransposable elements (TEs) occupy nearly 50% of mammalian genomes and are both potential dangers to genome stability and functional genetic elements. TEs can be expressed and exonised as part of a transcript, however, their full contribution to the transcript splicing remains unresolved. Here, guided by long and short read sequencing of RNAs, we show that 26% of coding and 65% of non-coding transcripts of human pluripotent stem cells (hPSCs) contain TEs. Different TE families have unique integration patterns with diverse consequences on RNA expression and function. We identify hPSC-specific splicing of endogenous retroviruses (ERVs) as well as LINE L1 elements into protein coding genes that generate TE-derived peptides. Finally, single cell RNA-seq reveals that proliferating hPSCs are dominated by ERV-containing transcripts, and subpopulations express SINE or LINE-containing transcripts. Overall, we demonstrate that TE splicing modulates the pluripotency transcriptome by enhancing and impairing transcript expression and generating novel transcripts and peptides.

scholarly journals 422Enrichment of cardiac differentiation of mouse pluripotent stem cells by beta 3 adrenoceptor stimulation

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S103-S103
Author(s):  
V Spinelli ◽  
L Sartiani ◽  
A Laurino ◽  
L Raimondi ◽  
M Calvani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation

scholarly journals Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew N. George ◽  
Karla F. Leavens ◽  
Paul Gadue
Keyword(s):  
Stem Cells ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Genetic Disease ◽  
Single Gene ◽  
Monogenic Diabetes ◽  
Human Pluripotent Stem Cells ◽  
Genetic Modifiers ◽  
Β Cell ◽  
Protein Coding

A mechanistic understanding of the genetic basis of complex diseases such as diabetes mellitus remain elusive due in large part to the activity of genetic disease modifiers that impact the penetrance and/or presentation of disease phenotypes. In the face of such complexity, rare forms of diabetes that result from single-gene mutations (monogenic diabetes) can be used to model the contribution of individual genetic factors to pancreatic β-cell dysfunction and the breakdown of glucose homeostasis. Here we review the contribution of protein coding and non-protein coding genetic disease modifiers to the pathogenesis of diabetes subtypes, as well as how recent technological advances in the generation, differentiation, and genome editing of human pluripotent stem cells (hPSC) enable the development of cell-based disease models. Finally, we describe a disease modifier discovery platform that utilizes these technologies to identify novel genetic modifiers using induced pluripotent stem cells (iPSC) derived from patients with monogenic diabetes caused by heterozygous mutations.

scholarly journals Rabbit induced pluripotent stem cells retain capability of in vitro cardiac differentiation

2019 ◽  
Vol 68 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Praopilas Phakdeedindan ◽  
Piyathip Setthawong ◽  
Narong Tiptanavattana ◽  
Sasitorn Rungarunlert ◽  
Praewphan Ingrungruanglert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Induced Pluripotent

Cardiac differentiation at an initial low density of human-induced pluripotent stem cells

2018 ◽  
Vol 54 (7) ◽  
pp. 513-522 ◽  
Author(s):  
Minh Nguyen Tuyet Le ◽  
Mika Takahi ◽  
Kenshiro Maruyama ◽  
Akira Kurisaki ◽  
Kiyoshi Ohnuma
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Low Density ◽  
Induced Pluripotent
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