scholarly journals Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/ -catenin, Activin/Nodal and BMP signaling

Development ◽  
2008 ◽  
Vol 135 (17) ◽  
pp. 2969-2979 ◽  
Author(s):  
T. Sumi ◽  
N. Tsuneyoshi ◽  
N. Nakatsuji ◽  
H. Suemori
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Bmp Signaling ◽  
Lineage Specification ◽  
Canonical Wnt

scholarly journals Bach1 regulates self-renewal and impedes mesendodermal differentiation of human embryonic stem cells

2019 ◽  
Vol 5 (3) ◽  
pp. eaau7887 ◽  
Author(s):  
Xiangxiang Wei ◽  
Jieyu Guo ◽  
Qinhan Li ◽  
Qianqian Jia ◽  
Qing Jing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Gene Promoters ◽  
Lineage Specification ◽  
Self Renewal ◽  
Polycomb Repressive Complex 2 ◽  
Direct Target ◽  
Processing Protease

The transcription factor BTB and CNC homology 1 (Bach1) is expressed in the embryos of mice, but whether Bach1 regulates the self-renewal and early differentiation of human embryonic stem cells (hESCs) is unknown. We report that the deubiquitinase ubiquitin-specific processing protease 7 (Usp7) is a direct target of Bach1, that Bach1 interacts with Nanog, Sox2, and Oct4, and that Bach1 facilitates their deubiquitination and stabilization via the recruitment of Usp7, thereby maintaining stem cell identity and self-renewal. Bach1 also interacts with polycomb repressive complex 2 (PRC2) and represses mesendodermal gene expression by recruiting PRC2 to the genes’ promoters. The loss of Bach1 in hESCs promotes differentiation toward the mesendodermal germ layers by reducing the occupancy of EZH2 and H3K27me3 in mesendodermal gene promoters and by activating the Wnt/β-catenin and Nodal/Smad2/3 signaling pathways. Our study shows that Bach1 is a key determinant of pluripotency, self-renewal, and lineage specification in hESCs.

scholarly journals Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Petter S. Woll ◽  
Julie K. Morris ◽  
Matt S. Painschab ◽  
Rebecca K. Marcus ◽  
Aimee D. Kohn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Human Embryonic Stem Cells ◽  
Stromal Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Human embryonic stem cells (hESCs) provide an important means to effectively study soluble and cell-bound mediators that regulate development of early blood and endothelial cells in a human model system. Here, several complementary methods are used to demonstrate canonical Wnt signaling is important for development of hESC-derived cells with both hematopoietic and endothelial potential. Analyses using both standard flow cy-tometry, as well the more detailed high-throughput image scanning flow cytometry, characterizes sequential development of distinct early developing CD34brightCD31+Flk1+ cells and a later population of CD34dimCD45+ cells. While the CD34brightCD31+Flk1+ have a more complex morphology and can develop into both endothelial cells and hematopoietic cells, the CD34dimCD45+ cells have a simpler morphology and give rise to only hematopoietic cells. Treatment with dickkopf1 to inhibit Wnt signaling results in a dramatic decrease in development of cells with hematoendothelial potential. In addition, activation of the canonical Wnt signaling pathway in hESCs by coculture with stromal cells that express Wnt1, but not use of noncanonical Wnt5-expressing stromal cells, results in an accelerated differentiation and higher percentage of CD34brightCD31+Flk1+ cells at earlier stages of differentiation. These studies effectively demonstrate the importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development.

scholarly journals Distinct Lineage Specification Roles for NANOG, OCT4, and SOX2 in Human Embryonic Stem Cells

2012 ◽  
Vol 10 (4) ◽  
pp. 440-454 ◽  
Author(s):  
Zheng Wang ◽  
Efrat Oron ◽  
Brynna Nelson ◽  
Spiro Razis ◽  
Natalia Ivanova
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Lineage Specification ◽  
Distinct Lineage

scholarly journals The Role of Sequential BMP Signaling in Directing Human Embryonic Stem Cells to Bipotential Gonadal Cells

2017 ◽  
Vol 102 (11) ◽  
pp. 4303-4314 ◽  
Author(s):  
Kirsi Sepponen ◽  
Karolina Lundin ◽  
Katri Knuus ◽  
Pia Väyrynen ◽  
Taneli Raivio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Academic Research ◽  
Embryonic Stem ◽  
Gonadal Development ◽  
Activin A ◽  
Bmp Signaling

Abstract Context Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but because of a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective To establish an in vitro method for studying differentiation of bipotential gonadal progenitors by using human embryonic stem cells (hESCs) and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation. Design We tested 17 protocols using activin A, CHIR-99021, and varying durations of BMP-7 and the BMP inhibitor dorsomorphin. Activation of activin A, WNT, and BMP pathways was optimized to induce differentiation. Setting Academic research laboratory. Main Outcomes Measures Cell differentiation, gene expression, and flow cytometry. Results The two most efficient protocols consistently upregulated IM markers LHX1, PAX2, and OSR1 at days 2 to 4 and bipotential gonadal markers EMX2, GATA4, WT1, and LHX9 at day 8 of culture. The outcome depended on the combination of the duration, concentration, and type of BMP activation and the length of WNT signaling. Adjusting any of the parameters substantially affected the requirements for other parameters. Conclusions We have established a reproducible protocol for directed differentiation of hESCs into bipotential gonadal cells. The protocol can be used to model early gonadal development in humans and allows further differentiation to mature gonadal somatic cells.

Role of BMP Signaling in Pancreatic Progenitor Differentiation from Human Embryonic Stem Cells

2013 ◽  
Vol 9 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Lina Sui ◽  
Mieke Geens ◽  
Karen Sermon ◽  
Luc Bouwens ◽  
Josué Kunjom Mfopou
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Bmp Signaling ◽  
Pancreatic Progenitor
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