Generation and trapping of a mesoderm biased state of human pluripotency
| Autor: | Jonathon Carr, Jason Wray, Chela James, Christopher J. Price, Jason A. Halliwell, Charlotta Böiers, Tariq Enver, John Brown, Dylan Stavish, Thomas J. R. Frith, Peter W. Andrews, Ivana Barbaric, Ingrid Saldaña-Guerrero |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Cell biology Mesoderm Science Cell Plasticity General Physics and Astronomy Biology Regenerative medicine Article General Biochemistry Genetics and Molecular Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine Cell Self Renewal medicine Animals Humans Compartment (development) Cell Lineage Induced pluripotent stem cell lcsh:Science Embryonic Stem Cells Multidisciplinary Cell Differentiation General Chemistry Cellular Reprogramming Culture Media 030104 developmental biology medicine.anatomical_structure Cell culture Differentiation MIXL1 lcsh:Q Stem cell 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Application of pluripotent cells in regenerative medicine requires an understanding of how they exit pluripotency. Here the authors demonstrate support for the idea that pluripotency exit involves pluripotent intermediates that exhibit lineage bias by identifying and trapping a mesoderm biased sub-state in culture. |
| Databáze: | OpenAIRE |
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