Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem  Cells

Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Andrew R. Bjorksten, Mirella Dottori, Donald F. Newgreen Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR and GD2, and confirmed their trunk-like HOX gene expression. We showed that continuing BMP4 and curtailing FGF2 in vitro, augmented with corticosteroid mimetic, induced these cells to upregulate the chromaffin cell-specific marker PNMT and other CA synthesis and storage markers, and we demonstrated noradrenaline and adrenaline by Faglu and high-performance liquid chromatography. We showed these human cells' SAP-like property of migration and differentiation into cells expressing chromaffin cell markers by implanting them into avian embryos in vivo and in chorio-allantoic membrane grafts. These cells have the potential for investigating differentiation of human chromaffin cells and for modeling diseases involving this cell type. Teaser In this article, Newgreen and colleagues show that human pluripotent cells can be induced to form chromaffin-like cells, whic...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research