RT Journal Article
SR Electronic
T1 An Epiblast Stem Cell derived multipotent progenitor population for axial extension
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 242461
DO 10.1101/242461
A1 Shlomit Edri
A1 Penny Hayward
A1 Peter Baillie-Johnson
A1 Ben Steventon
A1 Alfonso Martinez Arias
YR 2018
UL http://biorxiv.org/content/early/2018/01/30/242461.abstract
AB During vertebrate embryogenesis, the body axis elongates posteriorly through a self renewing population of precursor cells in the tail bud.The Caudal Lateral Epiblast (CLE) of the mammalian embryo harbours a stem cell/progenitor zone of bipotent progenitors that contribute to both the elongating spinal cord and the paraxial mesoderm of the embryo. These progenitors, called the Neural Mesodermal Progenitors (NMPs), are characterized by the coexpression of Sox2 and T. A number of in vitro studies have been able to produce NMP-like (NMP-l) cells from Pluripotent Stem Cells (PSCs). However, in contrast with embryonic NMPs these in vitro derived ones do not self renew. Here we use different protocols for NMP-l cells and find that, in addition to NMPs, all produce cells with the potential to differentiate into Lateral Plate and Intermediate Mesoderm precursors. We show that Epiblast Stem Cells (EpiSCs) are a better starting source to produce NMPs and show that a specific differentiation protocol yields cells with the potential to self renew in vitro and to make large contributions in xenotransplant assay to axial elongation in both neural and mesodermal tissue. These cells are derived from a population that resembles the Caudal Epiblast (CE) of the embryo at the time of the appearance of the node and we show that a balance between Nodal and BMP signalling is important to define this population. Our study suggests that at the end of gastrulation and associated with the node, a multipotential progenitor population emerges that will give rise to the spinal cord and the mesodermal populations posterior to the brain.