Expression of the erythropoietin receptor by germline-derived cells - further support for a potential developmental link between the germline and hematopoiesis.

Malwina Suszynska,Agata Poniewierska-Baran,Janina Ratajczak,Krzysztof Marycz,Pranesh Gunjal,Magda Kucia,Mariusz Z Ratajczak,Sham S Kakar

doi:10.1186/1757-2215-7-66

Abstract

BackgroundExpressing several markers of migrating primordial germ cells (PGCs), the rare population of quiescent, bone marrow (BM)-residing very small embryonic-like stem cells (VSELs) can be specified like PGCs into hematopoietic stem/progenitor cells (HSPCs). These two properties of VSELs support the possibility of a developmental origin of HSPCs from migrating PGCs.MethodsTo address a potential link between VSELs and germ line cells we analyzed by RT-PCR and FACS expression of erythropoietin receptor (EpoR) on murine bone marrow- and human umbilical cord blood-derived VSELs, murine and human teratocarcinoma cell lines and human ovarian cancer cells. A proper gating strategy and immunostaining excluded from FACS analysis potential contamination by erythroblasts. Furthermore, the transwell chemotaxis assays as well as adhesion and signaling studies were performed to demonstrate functionality of erythropoietin - EpoR axes on these cells.ResultsWe report here that murine and human VSELs as well as murine and human teratocarcinoma cell lines and ovarian cancer cell lines share a functional EpoR.ConclusionsOur data provide more evidence of a potential developmental link between germline cells, VSELs, and HSCs and sheds more light on the developmental hierarchy of the stem cell compartment in adult tissues.

Highlights

The recent hot debate over the existence of developmentally primitive stem cells in bone marrow (BM) with broad differentiation potential has been fueled by the challenge these cells pose to the accepted hierarchy within the stem cell compartment of hematopoietic tissues [1]
Several papers have described the sharing of chromosomal aberrations between germline tumors and leukemias or lymphomas, which suggests their clonal origin [8,9,10]. It has been demonstrated in in vitro cultures that murine primordial germ cells (PGCs) isolated from embryos, stem cells isolated from murine testes [4], and teratocarcinoma cell lines can be specified into hematopoietic stem/progenitor cells (HSPCs) [11]
Animals were sacrificed, and we analyzed the number of very small embryonic-like stem cells (VSELs) and hematopoietic stem cells (HSCs) in the cell cycle according to BrdU incorporation as detected by FACS (Figure 1 panel A)

Summary

Introduction

The recent hot debate over the existence of developmentally primitive stem cells in bone marrow (BM) with broad differentiation potential has been fueled by the challenge these cells pose to the accepted hierarchy within the stem cell compartment of hematopoietic tissues [1]. Our recent work demonstrated the presence of small, quiescent, Sca-1+Lin−CD45− stem cells in adult murine BM and small CD133+Lin−CD45− cells in human BM and umbilical cord blood (UCB) [12,13,14,15,16] These cells, under appropriate co-culture conditions with OP-9 stromal cells, can be specified into HSPCs [17], and, based on the presence of a primitive type of chromatin in their nuclei as well as expression of embryonic stem cell markers such as Oct-4 and Nanog, these small cells were named very small embryonic-like stem cells (VSELs).

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Results

Conclusion