Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression

Mohamed A.E. Ali, Kyoko Fuse, Yuko Tadokoro, Takayuki Hoshii, Masaya Ueno, Masahiko Kobayashi, Naho Nomura, Ha Thi Vu, Hui Peng, Ahmed M. Hegazy, Masayoshi Masuko, Hirohito Sone, Fumio Arai, Atsushi Tajima, Atsushi Hirao

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抜粋

Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFPhigh cells exhibited significantly higher repopulating capacity than NS-GFPlow cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFPhigh cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34+ cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.

元の言語英語
記事番号11442
ジャーナルScientific reports
7
発行部数1
DOI
出版物ステータス出版済み - 12 1 2017

All Science Journal Classification (ASJC) codes

  • General

フィンガープリント Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Ali, M. A. E., Fuse, K., Tadokoro, Y., Hoshii, T., Ueno, M., Kobayashi, M., Nomura, N., Vu, H. T., Peng, H., Hegazy, A. M., Masuko, M., Sone, H., Arai, F., Tajima, A., & Hirao, A. (2017). Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression. Scientific reports, 7(1), [11442]. https://doi.org/10.1038/s41598-017-11909-3