Fetal liver: an ideal niche for hematopoietic stem cell expansion
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Fetal liver (FL) is an intricate and highly vascularized hematopoietic organ, which can support the extensive expansion of hematopoietic stem cells (HSCs) without loss of stemness, as well as of the downstream lineages of HSCs. This powerful function of FL largely benefits from the niche (or microenvironment), which provides a residence for HSC expansion. Numerous studies have demonstrated that the FL niche consists of heterogeneous cell populations that associate with HSCs spatially and regulate HSCs functionally. At the molecular level, a complex of cell extrinsic and intrinsic signaling network within the FL niche cells maintains HSC expansion. Here, we summarize recent studies on the analysis of the FL HSCs and their niche, and specifically on the molecular regulatory network for HSC expansion. Based on these studies, we hypothesize a strategy to obtain a large number of functional HSCs via 3D reconstruction of FL organoid ex vivo for clinical treatment in the future.
Keywordsfetal liver niche hematopoietic stem cell expansion signaling network
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We thank lab members for helpful discussions and critical reading of the paper. This work was supported by the National Natural Science Foundation of China (81530004, 31425016), the Ministry of Science and Technology of China (2016YFA0100500) and the Strategic Priority Research Program of the Chinese Academy of Sciences, China (XDA16010104).
- Gerhardt, D.M., Pajcini, K.V., D’altri, T., Tu, L., Jain, R., Xu, L., Chen, M. J., Rentschler, S., Shestova, O., Wertheim, G.B., et al. (2014). The Notch1 transcriptional activation domain is required for development and reveals a novel role for Notch1 signaling in fetal hematopoietic stem cells. Genes Dev 28, 576–593CrossRefPubMedPubMedCentralGoogle Scholar
- Krosl, J., Mamo, A., Chagraoui, J., Wilhelm, B.T., Girard, S., Louis, I., Lessard, J., Perreault, C., and Sauvageau, G. (2010). A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations. Blood 116, 1678–1684CrossRefPubMedPubMedCentralGoogle Scholar
- Lin, M.I., Price, E.N., Boatman, S., Hagedorn, E.J., Trompouki, E., Satishchandran, S., Carspecken, C.W., Uong, A., DiBiase, A., Yang, S., et al. (2015). Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. eLife 4, e05544CrossRefPubMedCentralGoogle Scholar
- Macosko, E.Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A.R., Kamitaki, N., Martersteck, E.M., et al. (2015). Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214CrossRefPubMedPubMedCentralGoogle Scholar
- Manesia, J.K., Xu, Z., Broekaert, D., Boon, R., van Vliet, A., Eelen, G., Vanwelden, T., Stegen, S., Van Gastel, N., Pascual-Montano, A., et al. (2015). Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways. Stem Cell Res 15, 715–721CrossRefPubMedGoogle Scholar
- Zeigler, F.C., Bennett, B.D., Jordan, C.T., Spencer, S.D., Baumhueter, S., Carroll, K.J., Hooley, J., Bauer, K., and Matthews, W. (1994). Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells. Blood 84, 2422–2430PubMedGoogle Scholar
- Zhao, X., Gao, F., Zhang, X., Wang, Y., Xu, L., Liu, K., Zhao, X., Chang, Y., Wei, H., Chen, H., et al. (2016). Improved clinical outcomes of rhGCSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSF-primed peripheral blood stem cell haploidentical transplantation: a multicenter study. Sci China Life Sci 59, 1139–1148CrossRefPubMedGoogle Scholar