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Pluripotent Stem Cells Retain Innate Species-specific Developmental Timing



Review of “Species-specific developmental timing is maintained by pluripotent stem cells ex utero” from Developmental Biology by Stuart P. Atkinson

Protocols for the differentiation of human pluripotent stem cells into useful cell types often look to developmental biology for clues. However, as cells of the developing human embryo differentiate over a 9-month period, in vitro differentiation protocols often call for extended periods of culture. Unfortunately, the long culture periods involved to form physiologically mature cells complicate the clinical application of pluripotent stem cell derivatives, and so, many labs are seeking a means to “speed up” differentiation protocols. 

As a first step towards this endeavor, researchers from the laboratory of James A. Thomson (Morgridge Institute for Research, Madison, USA) set out to assess if in vitro differentiation of pluripotent stem cells from different species reflects species-specific developmental timing. Their new study, published in Developmental Biology, now provides proof that pluripotent stem cells retain innate species-specific developmental timing and may represent a starting point in the effort to produce mature human cells in a quick and easy manner [1].

To assess species-specific rates of differentiation, the authors compared neural differentiation of two developmentally similar pluripotent stem cell types from different species - mouse epiblast stem cells (EpiSCs) and human embryonic stem cells (ESCs). Gene expression analysis employed Dynamic Time Warping, a novel technique that compares two independent time series that share similar patterns operating at different speeds, as well as Pearson correlation analyses

Fascinatingly, the results indicated that mouse EpiSCs always expressed neural-specific marker genes before their gene counterparts in human ESCs and that mouse EpiSCs differentiated more rapidly than human ESCs on a global level. These findings held true for both directed in vitro neural differentiation and neural differentiation in teratomas following injection of EpiSCs/ESCs into immunocompromised mice; this despite the presence of other germ layers and the mouse host. Lastly, the study also noted that the rates of neural differentiation in vitro mirrored those of Carnegie stage embryo progression in utero in a species-specific manner.

This all suggests that pluripotent stem cells retain innate species-specific developmental timing when differentiated in vitro. The next stage is to assess the mechanisms that control this innate timing and to discover whether we can speed up the clock and thereby reduce the time needed to get therapeutically relevant cells from human pluripotent stem cells to patients.

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  1. Barry C, Schmitz MT, Jiang P, et al. Species-specific developmental timing is maintained by pluripotent stem cells ex utero. Developmental Biology 2017;423:101-110.