Programming Pluripotent Precursor Cells Derived from Xenopus Embryos to Generate Specific Tissues and Organs

Abstract

Xenopus embryos provide a rich source of pluripotent cells that can be differentiated into functional organs. Since the molecular principles of vertebrate organogenesis appear to be conserved between Xenopus and mammals, this system can provide useful guidelines for the directional manipulation of human embryonic stem cells. Pluripotent Xenopus cells can be easily isolated from the animal pole of blastula stage Xenopus embryos. These so called “animal cap” cells represent prospective ectodermal cells, but give rise to endodermal, mesodermal and neuro-ectodermal derivatives if treated with the appropriate factors. These factors include evolutionary conserved modulators of the key developmental signal transduction pathways that can be supplied either by mRNA microinjection or direct application of recombinant proteins. This relatively simple system has added to our understanding of pancreas, liver, kidney, eye and heart development. In particular, recent studies have used animal cap cells to generate ectopic eyes and hearts, setting the stage for future work aimed at programming pluripotent cells for regenerative medicine.

Retinoic acid induced expression of Hnf1β and Fzd4 is required for pancreas development in Xenopus laevis

“…The same group also used early embryonic ectodermal explants to promote the formation of pancreatic tissue by treatment with a combination of activin and RA ( Moriya et al, 2000b ). A similar result was obtained by programming the same type of explant with a cocktail including VegT, Noggin and RA ( Chen et al, 2004 ; Borchers and Pieler, 2010 ). This same protocol, which was also utilised in the current study, aims to mimic early key regulatory events, given that RA signalling together with inhibition of BMP activity makes it possible to convert ventral endomesodermal explants from gastrula-stage Xenopus embryos to a pancreatic fate ( Pan et al, 2007 ).…”

Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates

“…However, for genes with higher expression in DMZ, the associated regulatory regions showed a similar accessibility signal in both explants, similar to what was observed at gsc and chrd. AC cells are considered pluripotent at the blastula stages and lose competence for mesoderm induction during gastrulation (Jones & Woodland, 1987;Borchers & Pieler, 2010). Consistent with the competence for mesoderm induction, mesoderm-expressed genes appear to exhibit accessible chromatin in AC.…”

Establishing pluripotency in early development

“…1). These cells are normally fated to give rise to ectoderm (epidermal ectoderm and neural ectoderm) but can also give rise to mesoderm and endoderm derivatives when exposed to specific factors [12]. …”