The topographical regulation of embryonic stem cell differentiation

Abstract

The potential use of pluripotent stem cells for tissue repair or replacement is now well recognized. While the ability of embryonic stem (ES) cells to differentiate into all cells of the body is undisputed, their use is currently restricted by our limited knowledge of the mechanisms controlling their differentiation. This review discusses recent work by ourselves and others investigating the intercellular signalling events that occur within aggregates of mouse ES cells. The work illustrates that the processes of ES cell differentiation, epithelialization and programmed cell death are dependent upon their location within the aggregates and coordinated by the extracellular matrix. Establishment of the mechanisms involved in these events is not only of use for the manipulation of ES cells themselves, but it also throws light on the ways in which differentiation is coordinated during embryogenesis.

Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes

“…These results also support the possibility that inhibition of apoptosis in the absence of a BM is caused by inhibition of the basal primitive ectoderm epithelialization by activation of the EMT cascade. This possibility is consistent with a previous suggestion by Murray and Edgar that the lack of cavitation in LAMC1 Ϫ/Ϫ EBs may result from the absence of polarized primitive ectoderm cells, because the initial stages of cavitation are associated with selective apoptosis of cells positioned at the apical surfaces of the newly formed columnar primitive ectoderm cells (12,49,50).…”

Trophoblast and hypoblast in the monotreme, marsupial and eutherian mammal: evolution and origins

“…Studies on induction of differentiation of EC and ES cells as embryoid bodies also suggest, by analogy with the isolated pluriblast experiments, that hypoblast delaminates on the exposed surface, and more is known about the molecular mechanisms involved in this process. (77) However, it is not at all clear what the relationship is between these two systems for studying cell allocation to the hypoblast lineage and in particular whether ES/EC cells are formally equivalent to pluriblast, to epiblast or to some in vitro derivative of epiblast. An alternative lineage-dependent explanation for hypoblast allocation suggests that since pluriblast allocation occurs in two waves, by successive differentiative divisions at the 8-to 16-cell and 16-to 32-cell transitions, (62) only the first (8-to 16-cell) division contributes to trophoblast, the second (16-to 32-cell) allocation contributing preferentially or exclusively to the hypoblast.…”

Genetic basis of human testicular germ cell cancer: insights from the fruitfly and mouse

“…Human and mouse ES cells share many features in common with EC cells and with embryonal germ (EG) cells, the derivatives of cultivated PGCs (Durcova-Hills et al 2001, 2003. ES cells are unable to colonise extraembryonic structures such as the yolk sac, trophectoderm and placenta (Robertson 1987;Nichols et al 1998;Hadjantonakis and Papaioannou 2001;Odorico et al 2001;Rossant 2001;Wobus 2001;Murray and Edgar 2004), suggesting that these structures arise from progenitor cells other than ES cells or that ES cells are totipotent initially but that manipulation in vitro destroys their totipotency.…”