Engineering a haematopoietic stem cell niche by revitalizing mesenchymal stromal cells.

ABSTRACT: Haematopoietic stem cells (HSCs) are maintained by bone marrow niches in vivo^1,2, but the ability of niche cells to maintain HSCs ex vivo is markedly diminished. Expression of niche factors by Nestin-GFP⁺ mesenchymal-derived stromal cells (MSCs) is downregulated upon culture, suggesting that transcriptional rewiring may contribute to this reduced HSC maintenance potential. Using an RNA sequencing screen, we identified five genes encoding transcription factors (Klf7, Ostf1, Xbp1, Irf3 and Irf7) that restored HSC niche function in cultured bone marrow-derived MSCs. These revitalized MSCs (rMSCs) exhibited enhanced synthesis of HSC niche factors while retaining their mesenchymal differentiation capacity. In contrast to HSCs co-cultured with control MSCs, HSCs expanded wi

SUBMITTER: Nakahara F 

PROVIDER: S-EPMC6499646 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature