Lectures and seminars Reconstitution of a soft bone marrow organoid for hematopoietic stem cell rejuvenation

08-12-2023 2:00 pm Add to iCal
Campus Solna Peter Richard Seminar Room, 3rd floor at Biomedicum

Reconstitution of a soft bone marrow organdie for hematopoietic stem cell rejuvenation

Speaker: Prof. Rui Yue, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche ex vivo remains unknown. Rui Yue’s lab has recently showed that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. Their study highlights biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow organoid for HSC rejuvenation.

Thomas Perlmann and Qiaolin Deng

Selected recent articles

Rui Yue

1.             Zhang XY#, Cao DD#, Xu LT#, Xu YH#, Gao ZH, Pan YZ, Jiang M, Wei YH, Wang LH, Liao Y, Wang QG, Yang L, Xu XC, Gao YW, Gao SR, Wang J, and Yue R, (2023). Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation. Cell Stem Cell. 30(4):378-395.e8.

2.             Sun, Y.#, Ma, M.#, Cao, D., Zheng, A., Zhang, Y., Su, Y., Wang, J., Xu, Y., Zhou, M., Tang, Y., Liu, Y., Ma, T., Fan, A., Zhang, X., Zhu, Q., Qin, J., Mo, C., Xu, Y., Zhang, L.*, Xu, D.*, and Yue, R.* (2023) Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP. Circulation Research 132, 586-600

3.             Wang, J., Zhu, Q., Cao, D., Peng, Q., Zhang, X., Li, C., Zhang, C., Zhou, B. O., and Yue, R. (2023) Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton. Proc Natl Acad Sci USA 120, e2203779120, No.1, Vol.120

4.             Mo, C.#, Guo J.#, Qin J., Zhang X., Sun Y., Wei H., Cao D., Zhang Y., Zhao C., Xiong Y., Zhang Y., Sun Y., Shen L.*, Yue, R.* (2022). Single-cell transcriptomics of LepR-positive skeletal cells reveals heterogeneous stress-dependent stem and progenitor pools. EMBO Journal e108415

5.             He, J.#, Yan, J.#, Wang, J.#, Zhao, L.#, Xin, Q.#, Zeng, Y., Sun, Y., Zhang, H., Bai, Z., Li, Z., Ni, Y., Gong, Y., Li, Y., He, H., Bian, Z., Lan, Y., Ma, C., Bian, L., Zhu, H.*, Liu, B.*, and Yue, R.* (2021). Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses. Cell Research 31,742-757