Clonal isolation of hESCs reveals heterogeneity within the pluripotent stem cell compartment

2006 ◽  
Vol 3 (10) ◽  
pp. 807-815 ◽  
Author(s):  
Morag H Stewart ◽  
Marc Bossé ◽  
Kristin Chadwick ◽  
Pablo Menendez ◽  
Sean C Bendall ◽  
...  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dylan Stavish ◽  
Charlotta Böiers ◽  
Christopher Price ◽  
Thomas J. R. Frith ◽  
Jason Halliwell ◽  
...  

Abstract We postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explore mesoderm lineage-bias within the human pluripotent stem cell compartment. We identify a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programmes. Functionally these cells initiate stem cell cultures and exhibit mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we ‘trap’ and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of ‘cross-antagonistic’ signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine.


2019 ◽  
Author(s):  
Dylan Stavish ◽  
Charlotta Böiers ◽  
Christopher Price ◽  
Thomas J R Frith ◽  
Jason Halliwell ◽  
...  

ABSTRACTWe postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explored mesoderm lineage-bias within the human pluripotent stem cell compartment. We identified a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programs. Functionally these cells could initiate stem cell cultures and exhibited mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we could ‘trap’ and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of ‘cross-antagonistic’ signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Soo-Zin Kim-Wanner ◽  
Seo-Youn Lee ◽  
Erhard Seifried ◽  
Halvard Bonig

Abstract Background Healthy volunteer registry donors have become the backbone of stem cell transplantation programs. While most registrants will never become actual donors, a small minority are called upon twice, most commonly for the same patient because of poor graft function. Anecdotal evidence provides no hard reasons to disallow second-time mobilized apheresis, but few centers have treated enough two-time donors for definitive conclusions. Moreover, for reasons unknown, the efficiency of G-CSF varies greatly between donations. Methods Comparison of outcomes of first vs. second donations can formally confirm G-CSF responsiveness as intrinsically, likely genetically, determined. In our database, we identified 60 donors (1.3%) who received two cycles of G-CSF 24 days to 4 years apart and systematically compared mobilization outcomes. Results First and second mobilization and collection proceeded without severe or unusual adverse effects. First-time mobilization efficiency was highly predictive of second-time mobilization. Neither mobilization efficiency nor time lag between donations affected the similarity of first- and second-time mobilization outcomes. Conclusions With the caveat that only donors with an unremarkable first donation were cleared for a second, our data indicate that a second donation is feasible, equally tolerable as a first donation, and efficient. Moreover, the data strongly support the notion of donor-intrinsic variables dictating mobilization response and argue against relevant damage to the stem cell compartment during mobilization with rhG-CSF.


2021 ◽  
Author(s):  
Sherwell Sanchez Carlos M. Abascal ◽  
Emily Lodge ◽  
Thea L. Willis ◽  
Mohammad K. Hajihosseini ◽  
Cynthia L. Andoniadou

2007 ◽  
Vol 104 (10) ◽  
pp. 4048-4053 ◽  
Author(s):  
C. D. Peacock ◽  
Q. Wang ◽  
G. S. Gesell ◽  
I. M. Corcoran-Schwartz ◽  
E. Jones ◽  
...  

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