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Research paper
Published online: 2021-11-22
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BMP4 is insufficient to differentiate umbilical cord mesenchymal stem cells into germ cell-like cells in vitro

Pengbo Wang1, Huanhuan Hu1, Xinyi Li1, Ruiyun Zhang1, Hongbin Cheng1, Haixia Qin1, Guojie Ji1, Huigen Feng1, Yanli Liu1, Juntang Lin1
DOI: 10.5603/GP.a2021.0144
Affiliations
  1. Xinxiang Medical University, Xinxiang, China

open access

Ahead of Print
ORIGINAL PAPERS Gynecology
Published online: 2021-11-22

Abstract

Objectives: Mesenchymal stem cell (MSC)-based therapies are expected to restore the fertility of infertile patients. In addition to MSC-derived paracrine effects to improve reproductive function, the differentiation of MSCs into germ cell (GC)-like cells is still a promising method to repair the injured reproductive system. The aim of this study was to examine the effect and potential mechanism of BMP4 in inducing umbilical cord MSC (UcMSC) transdifferentiation into GC-like cells.

Material and methods: UcMSCs were isolated, cultured and identified by flow cytometry and multilineage differentiation assays. After induction with 12.5 ng/mL BMP4 for 21 days, UcMSCs were collected for further examination. Immunofluorescence was used to detect the expression of Prdm1 and Prdm14; RT-PCR and RNA sequencing were used to detect differential gene expression (DEGs).

Results: The morphology of UcMSCs became large and flat after treatment with BMP4; the expression of GC-related genes (OCT4, Prdm1, Ifitm3 and Stella) was significantly downregulated, and further immunofluorescence results also confirmed the significant downregulation of Prdm1 in UcMSCs with BMP4 induction, while the expression of Prdm14 was significantly upregulated. The results of RNA sequencing and further analysis revealed no explicit correlation between BMP4 induction and the differentiation of UcMSCs into GC-like cells based on the 662 screened DEGs in UcMSCs with or without BMP4 induction.

Conclusions: The differentiation of MSCs into GC-like cells is rather complex, and BMP4 alone is insufficient to induce UcMSCs to differentiate into GC-like cells, regardless of protein level or gene expression level.

Abstract

Objectives: Mesenchymal stem cell (MSC)-based therapies are expected to restore the fertility of infertile patients. In addition to MSC-derived paracrine effects to improve reproductive function, the differentiation of MSCs into germ cell (GC)-like cells is still a promising method to repair the injured reproductive system. The aim of this study was to examine the effect and potential mechanism of BMP4 in inducing umbilical cord MSC (UcMSC) transdifferentiation into GC-like cells.

Material and methods: UcMSCs were isolated, cultured and identified by flow cytometry and multilineage differentiation assays. After induction with 12.5 ng/mL BMP4 for 21 days, UcMSCs were collected for further examination. Immunofluorescence was used to detect the expression of Prdm1 and Prdm14; RT-PCR and RNA sequencing were used to detect differential gene expression (DEGs).

Results: The morphology of UcMSCs became large and flat after treatment with BMP4; the expression of GC-related genes (OCT4, Prdm1, Ifitm3 and Stella) was significantly downregulated, and further immunofluorescence results also confirmed the significant downregulation of Prdm1 in UcMSCs with BMP4 induction, while the expression of Prdm14 was significantly upregulated. The results of RNA sequencing and further analysis revealed no explicit correlation between BMP4 induction and the differentiation of UcMSCs into GC-like cells based on the 662 screened DEGs in UcMSCs with or without BMP4 induction.

Conclusions: The differentiation of MSCs into GC-like cells is rather complex, and BMP4 alone is insufficient to induce UcMSCs to differentiate into GC-like cells, regardless of protein level or gene expression level.

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Keywords

Germ cell; Mesenchymal stem cell; Bone morphogenetic protein 4; Fertility

About this article
Title

BMP4 is insufficient to differentiate umbilical cord mesenchymal stem cells into germ cell-like cells in vitro

Journal

Ginekologia Polska

Issue

Ahead of Print

Article type

Research paper

Published online

2021-11-22

DOI

10.5603/GP.a2021.0144

Keywords

Germ cell
Mesenchymal stem cell
Bone morphogenetic protein 4
Fertility

Authors

Pengbo Wang
Huanhuan Hu
Xinyi Li
Ruiyun Zhang
Hongbin Cheng
Haixia Qin
Guojie Ji
Huigen Feng
Yanli Liu
Juntang Lin

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