Lei Ding, Ph.D.
Hematopoietic stem cells (HSCs) play critical roles in the generation, repair and homeostasis of the blood and immune system via self-renewal and multilineage differentiation. They are maintained for life through self-renewing divisions where HSCs divide to produces HSC daughter cells. How self-renewal is regulated is a central question in stem cell biology. HSC self-renewal is regulated by both HSC intrinsic and extrinsic mechanisms. In vivo,
HSCs reside in a complex microenvironment and are critically regulated by factors secreted by cells that comprise a specialized niche. The HSC niche represents a critical element responsible for the extrinsic regulation of HSC self-renewal. Alterations to the microenvironment can contribute to the development of leukemia, bone marrow failure syndromes and anemia. We are investigating extrinsic mechanisms that regulate HSC self-renewal, and how mis-regulation of niche/HSC interactions contributes to diseases such as cancer and anemia. Understanding the HSC niche is a key step in helping design better strategies for in vitro
expansion of HSCs, and for treatment of niche related diseases such as leukemia and anemia.
- Decker, M., Leslie, J., Liu, Q. and Ding, L. (2018) Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance. Science 360: 106-110.
- Jeong, M., Park, H.J., Celik, H., Ostrander, E.L., Reyes, J.M., Guzman, A., Rodriguez, B., Lei, Y., Lee, Y., Ding, L., Guryanova, O.A., Li, W., Goodell, M.A., Challen, G.A. (2018) Loss of Dnmt3a immortalizes hematopoietic stem cells in vivo. Cell Reports 23: 1-10.
- Sarkaria, S.M., Decker, M. and Ding, L. (2018) Bone marrow micro-environment in normal and deranged hematopoiesis: Opportunities for regenerative medicine and therapies. BioEssays 40 doi: 10.1002/bies.201700190. Epub 2018 Jan 31.
- Hirata, Y., Furuhashi, K., Ishii, H., Li, H.W., Pinho, S., Ding, L., Robson, S.C., Frenette, P.S. and Fujisaki, J. (2018) CD150high bone marrow Tregs maintain hematopoietic stem cell quiescence and immune privilege via adenosine. Cell Stem Cell 22: 445-453.
- Lee, Y., Decker, M., Lee, H. and Ding L. (2017) Extrinsic regulation of hematopoietic stem cells in development, homeostasis and diseases. Wiley Interdiscip. Rev. Dev. Biol. doi: 10.1002/wdev.279.
- Park, D.Y., Lee, J., Kim, J., Kim, K., Hong, S., Han, S., Kubota, Y., Augustin, H.G., Ding, L., Kim, J.W., Kim, H., He, Y., Adams, R.H. and Koh, G.Y. (2017) Plastic roles of pericytes in the blood-retinal barrier. Nature Communications 8: 15296.
- Decker, M., Martinez-Morentin, L., Wang, G., Lee, Y., Liu, Q., Leslie, J. and Ding, L. (2017) Leptin-receptor-expressing bone marrow stromal cells are myofibroblasts in primary myelofibrosis. Nature Cell Biology 19: 677-688.
- Ding, L. (2017) HSC niche: ample room for every guest stem cell. Blood 129: 2042-2043.
- Jiang, N., Chen, M., Yang, G., Xiang, L., He, L., Hei, T.K., Chotkowski, G., Tarnow, D.P., Finkel, M., Ding, L., Zhou, Y. and Mao, J.J. (2016) Hematopoietic stem cell in neural-crest derived bone marrow. Scientific Reports 6: 36411.
- Sawai, C.M., Babovic, S., Upadhaya, S., Knapp, D.J., Lavin, Y., Lau, C.M., Goloborodko, A., Feng, J., Fujisaki, J., Ding, L., Mirny, L.A., Merad, M., Eaves, C.J. and Reizis, B. (2016) Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity doi: 10.1016/j.immuni.2016.08.007.
- Zhou, B.*, Ding, L.*# and Morrison, S.J.# (2015) Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1. Elife 4: e05521. (*equal contribution, #co-corresponding)
- Hayakawa, Y., Ariyama, H., Stancikova, J., Sakitani, K., Asfaha, S., Renz, B.W., Dubeykovskaya, Z.A., Shibata, W., Wang, H., Westphalen, C.B., Chen, X., Takemoto, Y., Kim, W., Khurana, S.S., Tailor, Y., Nagar, K., Tomita, H., Hara, A., Sepulveda, A.R., Setlik, W., Gershon, M.D., Saha, S., Ding, L., Shen, Z., Fox, J.G., Friedman, R.A., Konieczny, S.F., Worthley, D.L., Korinek, V. and Wang, T.C. (2015) Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche. Cancer Cell 28: 800-814.
- Burberry, A., Zeng, M.Y., Ding, L., Wicks, I., Inohara, N., Morrison, S.J. and Nunez, G. (2014) Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and Toll-like receptor signaling. Cell Host Microbe 15: 779-791.
- Chaix, J., Nish, S.A., Lin, W.H., Rothman, N.J., Ding, L., Wherry, E.J. and Reiner, S.L. (2014) Cutting edge: CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal. J. Immunol. 193: 1013-1016.
- Oguro, H., Ding, L. and Morrison, S.J. (2013) SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell 13: 102-116.
- Ding, L. and Morrison, S. (2013) Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature dpi:10.1038. Published online Feb 24, 2013.
- Ding, L., Saunders, T., Enikolopov, G. and Morrison, S. (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481: 457-462
- Ding, L. and Han, M. (2007) GW182 family proteins are critical for miRNA-mediated gene silencing. Trends in Cell Biology 17: 411-416.
- Zhang, L.*, Ding, L.*, Cheung, T., Dong, M., Chen, J., Sewell, A., Liu, X., Yates, J. and Han, M. (2007) Systematic identification of miRISC proteins, miRNAs, and their mRNA targets in C. elegans by their interactions with GW182 family proteins AIN-1 and AIN-2. Molecular Cell 28: 598-613 (*equal contribution)
- Ding, L., Spencer, A., Morita, K. and Han, M. (2005). The developmental timing regulator AIN-1 interacts with argonaute protein ALG-1, miRISCs and may target ALG-1 to cytoplasmic P bodies in C. elegans. Molecular Cell 19: 437-447.