scholarly journals Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sandra Heller ◽  
Zhijian Li ◽  
Qiong Lin ◽  
Ryan Geusz ◽  
Markus Breunig ◽  
...  

AbstractCell type specification during pancreatic development is tightly controlled by a transcriptional and epigenetic network. The precise role of most transcription factors, however, has been only described in mice. To convey such concepts to human pancreatic development, alternative model systems such as pancreatic in vitro differentiation of human pluripotent stem cells can be employed. Here, we analyzed stage-specific RNA-, ChIP-, and ATAC-sequencing data to dissect transcriptional and regulatory mechanisms during pancreatic development. Transcriptome and open chromatin maps of pancreatic differentiation from human pluripotent stem cells provide a stage-specific pattern of known pancreatic transcription factors and indicate ONECUT1 as a crucial fate regulator in pancreas progenitors. Moreover, our data suggest that ONECUT1 is also involved in preparing pancreatic progenitors for later endocrine specification. The dissection of the transcriptional and regulatory circuitry revealed an important role for ONECUT1 within such network and will serve as resource to study human development and disease.

2020 ◽  
Vol 38 (4) ◽  
pp. 460-470 ◽  
Author(s):  
Nathaniel J. Hogrebe ◽  
Punn Augsornworawat ◽  
Kristina G. Maxwell ◽  
Leonardo Velazco-Cruz ◽  
Jeffrey R. Millman

2012 ◽  
Vol 349 (3) ◽  
pp. 809-824 ◽  
Author(s):  
Toshihiko Ezashi ◽  
Bhanu Prakash V. L. Telugu ◽  
R. Michael Roberts

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
In Young Choi ◽  
Hotae Lim ◽  
Hyeon Jin Cho ◽  
Yohan Oh ◽  
Bin-Kuan Chou ◽  
...  

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/).


MicroRNA ◽  
2014 ◽  
Vol 3 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Natalie Francis ◽  
Melanie Moore ◽  
Guy Rutter ◽  
Chris Burns

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Abdullah J. Alshawaf ◽  
Ana Antonic ◽  
Efstratios Skafidas ◽  
Dominic Chi-Hung Ng ◽  
Mirella Dottori

Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ken Hiratsuka ◽  
Toshiaki Monkawa ◽  
Tomohiko Akiyama ◽  
Yuhki Nakatake ◽  
Mayumi Oda ◽  
...  

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