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 Generation of functional ciliates cholangiocytes from human pluripotent stem cells

2021 ◽  
Author(s):  
Mina Ogawa ◽  
Jia-Xin Jiang ◽  
Sunny Xia ◽  
Donghe Yang ◽  
Avrilynn Ding ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bile Duct ◽  
Pluripotent Stem Cells ◽  
Primary Cilia ◽  
Human Pluripotent Stem Cells ◽  
Biliary Disease ◽  
New Strategy ◽  
Immunocompromised Mice ◽  
And Function

The derivation of mature functional cholangiocytes from human pluripotent stem cells (hPSCs) would provide a model for studying the pathogenesis of cholangiopathies and for developing novel therapies to treat them. Current differentiation protocols are not efficient and give rise to cholangiocytes that are not fully mature, limiting their therapeutic applications. Here, we describe a new strategy to generate functional hPSC-derived cholangiocytes that display many characteristics of mature bile duct cells including high levels of CFTR and the presence of a primary cilia capable of sensing flow. With this level of maturation, these cholangiocytes are amenable for testing the efficacy of new cystic fibrosis drugs and for studying the role of cilia in cholangiocyte development and function. Transplantation studies showed that the mature cholangiocytes generate ductal structures in the liver of immunocompromised mice providing the first indication that it may be possible to develop cell based therapies to restore bile duct function in patients with biliary disease.

Abstract 65: Latrophilin-2 is a Specific Cell-surface Marker for Cardiac Progenitor Cells and Specifies Cardiac Lineage Commitment and Development

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Hyun-Jai Cho ◽  
Choon-Soo Lee ◽  
Jin-Woo Lee ◽  
Jung-Kyu Han ◽  
Han-Mo Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Development ◽  
Cardiac Differentiation ◽  
Specific Cell ◽  
Specific Marker ◽  
Cardiac Progenitor Cells ◽  
Cardiac Lineage

Backgrounds: The identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is utilized to isolate a certain cell type with high purity for the therapeutic purpose. We here report a new cardiac-specific marker, and demonstrate its functional significance in the cardiac development. Methods and Results: When mouse pluripotent stem cells (ES and iPS cells) were stimulated with BMP4, Activin A, bFGF and VEGF, they differentiated into cardiac cells. To screen cell-surface expressing molecules on cardiac progenitor cells compared to undifferentiated mouse iPS and ES cells, we isolated Flk1+/PDGFRa+ cells at differentiation day 4 and performed microarray analysis. Among candidates, we identified a new G protein-coupled receptor, Latrophilin-2 (LPHN2) whose signaling pathway and its effect on cardiac differentiation is unknown. In sorting experiments under cardiac differentiation condition, LPHN2+ cells derived from pluripotent stem cells strongly expressed cardiac-related genes (Mesp1, Nkx2.5, aMHC and cTnT) and exclusively gave rise to beating cardiomyocytes, as compared with LPHN2- cells. LPHN2-/- mice revealed embryonically lethal and huge defects in cardiac development. Interestingly, LPHN2+/- heterozygotes were alive and fertile. For the purpose of cardiac regeneration, we transplanted iPS-derived LPHN2+ cells into the infarcted heart of adult mice. LPHN2+ cells differentiated into cardiomyocytes, and systolic function of left ventricle was improved and infarct size was reduced. We confirmed LPHN2 expression on human iPS and ES cell-derived cardiac progenitor cells and human heart. Conclusions: We demonstrate that LPHN2 is a functionally significant and cell-surface expressing marker for both mouse and human cardiac progenitor and cardiomyocytes. Our findings provide a valuable tool for isolating cardiac lineage cells from pluripotent stem cells and an insight into cardiac development and regeneration.

scholarly journals Genome-wide Screen for Culture Adaptation and Tumorigenicity-Related Genes in Human Pluripotent Stem Cells

iScience ◽  
2019 ◽  
Vol 11 ◽  
pp. 398-408 ◽  
Author(s):  
Uri Weissbein ◽  
Mordecai Peretz ◽  
Omer Plotnik ◽  
Ofra Yanuka ◽  
Ido Sagi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Culture Adaptation ◽  
Genome Wide

RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells

2020 ◽  
Vol 52 (9) ◽  
pp. 931-938 ◽  
Author(s):  
Yicheng Long ◽  
Taeyoung Hwang ◽  
Anne R. Gooding ◽  
Karen J. Goodrich ◽  
John L. Rinn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
And Function

scholarly journals Culture Conditions Affect Cardiac Differentiation Potential of Human Pluripotent Stem Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48659 ◽  
Author(s):  
Marisa Ojala ◽  
Kristiina Rajala ◽  
Mari Pekkanen-Mattila ◽  
Marinka Miettinen ◽  
Heini Huhtala ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Conditions ◽  
Human Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Differentiation Potential

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 Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
In Young Choi ◽  
Hotae Lim ◽  
Hyeon Jin Cho ◽  
Yohan Oh ◽  
Bin-Kuan Chou ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Human Pluripotent Stem Cells ◽  
Knock Out ◽  
Muscle Progenitor Cells ◽  
Transcriptional Landscape

Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).

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