Abstract

The purpose of this study was to investigate the immunophenotypes and gene expression profile of high proliferative placenta-derived multipotent cells (PDMCs) population at different stages of culture. We demonstrated that the colonies resulting from single cells were either positive or negative for CK7, whereas only PDMC clones with weak CK7 expression (CK7low-clones) were highly proliferative. Interestingly, vimentin positive (Vim+) placental stromal mesenchymal cells did not express CK7 in situ, but double CK7+Vim+ cells detection in tissue explants and explants outgrowth indicated CK7 inducible expression in vitro. PCNA presence in CK7+Vim+ cells during placental explants culturing confirmed belonging of these cells to proliferative subpopulation. Transcription factors CDX2 and EOMES were expressed in both CK7low-clones and subset of stromal mesenchymal cells of first-trimester placental tissue in situ. Meanwhile, CK7low -clones and stromal mesenchymal cells of full-term placental tissue in situ expressed ERG heterogeneously. SPP1, COL2A1, and PPARG2 mesodermal-related genes expression by CK7low-clones additionally confirms their mesenchymal origin. Inherent stem cell-related gene expression (IFTM3, POU5F1, and VASA) in CK7low-clones might indicate their enrichment for progenitors. Finally, in CK7low-clones we observed expression of such trophoblast-associated genes as CGB types I and II, fusogenic ERVW-1, GCM1, and GATA3. Thus, our results indicate that PDMCs acquired the representative immunophenotype signature under culture conditions.

Highlights

  • Human placenta contains populations of different stem cell types, namely, the mesenchymal stem/stromal cells (MSC) [1], trophoblast stem cells [2], hematopoietic stem cells [3], and endothelial progenitor cells [4]

  • We showed that cytokeratins appeared in placenta-derived multipotent cells (PDMCs) in vitro, their expression was previously detected in umbilical cord-derived MSCs and in stromal cells of different compartments of umbilical cord in situ [22]

  • We have demonstrated that PDMCs and CK7low-clones expressed the following trophoblast-associated genes: GATA, glial cell missing-1 (GCM), ERVW, and chorionic gonadotropin beta (CGB)

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Summary

Introduction

Human placenta contains populations of different stem cell types, namely, the mesenchymal stem/stromal cells (MSC) [1], trophoblast stem cells [2], hematopoietic stem cells [3], and endothelial progenitor cells [4]. Based on pericyte markers CD146 and NG2 expression, the perivascular origin of foetal placental MSCs has been hypothesized [1, 3]. CK7 was expressed in both adult hematopoietic stem cells and fetal liver (CD150+KSL) ones in vivo [10]. BioMed Research International mesenchymal stromal cells differ in expression of cytokeratins. Based on the heterogeneity of the placenta-derived multipotent cells (PDMCs) the expression of cytokeratins in the subset of placental mesenchymal progenitors remains unclear

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