scholarly journals Genetic Engineering of Human Embryonic Stem Cells for Precise Cell Fate Tracing during Human Lineage Development

2018 ◽  
Vol 11 (5) ◽  
pp. 1257-1271 ◽  
Author(s):  
Zhenyu Chen ◽  
Xudong Ren ◽  
Xiangjie Xu ◽  
Xiaojie Zhang ◽  
Yi Hui ◽  
...  
2009 ◽  
Vol 218 (3) ◽  
pp. 455-459 ◽  
Author(s):  
David Nury ◽  
Tui Neri ◽  
Michel Pucéat

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Mickie Bhatia

Abstract The most common human cell-based therapy applied today is hematopoietic stem cell (HSC) transplantation. HSCs can be defined by two essential properties: self-renewal and multilineage hematopoietic differentiation. These combined HSC properties allow them to differentiate into all blood cell types (multilineage) in a sustained manner for the lifetime of the animal, which requires their ability to make cellular copies of themselves (self-renewal). These features can be tested by transplantation from donor to recipient and provide a functional basis to define and identify HSCs. Currently, human bone marrow (BM), mobilized peripheral blood, and umbilical cord blood (CB) represent the major sources of transplantable HSCs, but their availability for use is limited by both quantity and compatibility. Although increasing evidence suggests that somatic HSCs can be expanded to meet current needs, their in vivo potential is concomitantly compromised after ex vivo culture. Pluripotent human embryonic stem cells (hESCs) may provide an alternative. hESCs possess indefinite proliferative capacity in vitro, and have been shown to differentiate into the hematopoietic cell fate, giving rise to erythroid, myeloid, and lymphoid lineages using a variety of differentiation procedures. In most cases, hESC-derived hematopoietic cells show similar clonogenic progenitor capacity and primitive phenotype to somatic sources of hematopoietic progenitors, but possess limited in vivo repopulating capacity when transplanted into immunodeficient mice. Although this suggests HSC function can be derived from hESCs, the efficiency and quality of these cells must be characterized using surrogate models for potential clinical applications.


2017 ◽  
Author(s):  
Anastasiia Nemashkalo ◽  
Albert Ruzo ◽  
Idse Heemskerk ◽  
Aryeh Warmflash

AbstractParacrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells (“μColonies”) to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions, BMP4 acts as morphogen, but this effect requires secondary signals and particular cell densities. We further find that a “community effect” enforces a common fate within μColonies both in the state of pluripotency and when cells are differentiated, and that this effect allows more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.Summary StatementWe quantitatively examined signaling and differentiation in hESC colonies of varying size treated with BMP4. We show that secondary signals result in morphogen and community effects that determine cell fates.


PLoS ONE ◽  
2009 ◽  
Vol 4 (6) ◽  
pp. e6082 ◽  
Author(s):  
Ludovic Vallier ◽  
Thomas Touboul ◽  
Zhenzhi Chng ◽  
Minodora Brimpari ◽  
Nicholas Hannan ◽  
...  

2006 ◽  
Vol 13 ◽  
pp. S39
Author(s):  
Andrew Wilber ◽  
Jonathan L. Linehan ◽  
Xinghui Tian ◽  
R. Scott McIvor ◽  
Dan S. Kaufman

2005 ◽  
Vol 14 (4) ◽  
pp. 367-377 ◽  
Author(s):  
Chen Xiong ◽  
Dong-Qi Tang ◽  
Chang-Qing Xie ◽  
Li Zhang ◽  
Ke-Feng Xu ◽  
...  

2016 ◽  
Vol 30 (17) ◽  
pp. 1991-2004 ◽  
Author(s):  
Yael Yoffe ◽  
Maya David ◽  
Rinat Kalaora ◽  
Lital Povodovski ◽  
Gilgi Friedlander ◽  
...  

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