Abstract
Author SummaryStem cells are providing insight into embryo development and offering new approaches to clinical and therapeutic research. In part this progress arises from “directed differentiation” – artificially controlling the types of cells produced from stem cells. Here we describe the directed differentiation of mouse and human pluripotent stem cells into cells of the spinal cord and paraxial mesoderm (the tissue that generates muscle and bone that is normally found adjacent to the spinal cord). During embryo development, spinal cord and paraxial mesoderm arise from a shared group of precursors known as neuromesodermal progenitors (NMPs). We show that signals to which NMPs are exposed in embryos can be used to generate NMPs from pluripotent stem cells in a dish. We define conditions for the conversion of these NMPs into either spinal cord or mesoderm cells. Using these conditions, we provide evidence that the decision between spinal cord and mesoderm involves a gene, Brachyury, that promotes mesoderm production by inhibiting spinal cord generation. Together the data illustrate how mimicking normal embryonic development allows the generation of specific cell types from stem cells and that this can be used to analyse cells that are otherwise difficult to study.
Highlights
The differentiation of embryonic stem cells (ESCs) to specific cell types offers insight into developmental mechanisms and has potential therapeutic applications
We describe the in vitro generation of bipotential neuromesodermal progenitors from both mouse and human pluripotent stem cells that are capable of producing posterior neural tissue and paraxial mesodermal tissue
This recapitulates the behaviour of neuromesodermal progenitor (NMP) residing in the caudal lateral epiblast (CLE) and node-streak border (NSB) [15,22] (Figure 6G)
Summary
The differentiation of embryonic stem cells (ESCs) to specific cell types offers insight into developmental mechanisms and has potential therapeutic applications. Exposing NPCs to retinoic acid (RA) results in the repression of anterior identity and the induction of genes that typify hindbrain and anterior spinal cord (cervical) identity [5] This has been taken as support for the idea that newly generated NPCs are by default anterior and are posteriorised by exposure to specific extrinsic signals [6,7]. It is notable, that RA is actively excluded in the progenitors of the posterior spinal cord after gastrulation [8] and that commonly used ESC differentiation protocols do not efficiently generate neural cells of the more posterior spinal cord such as thoracic and lumbar spinal cord cells marked by posterior Hox gene expression, including Hoxc expression [9]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call