Lei Ding, Ph.D.

Gurewitsch and Vidda Foundation Associate Professor of Microbiology & Immunology and Rehabilitation & Regenerative Medicine
Ph.D., University of Colorado at Boulder

Mechanisms, particularly cell-extrinsic mechanisms, that regulate hematopoietic stem cell function

Research
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. 

We are interested in recruiting motivated graduate students, postdocs and technicians.

Selected Publications

1. Gao, L., Lee, H., Goodman, J. and Ding, L. (2024) Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program. Cell 187: 2801-2816. https://doi.org/10.1016/j.cell.2024.03.032

2. Hirakawa, H., Gao, L., Tavakol D.N., Vunjak-Novakovic, G. and Ding, L. (2023) Cellular plasticity of the bone marrow niche promotes hematopoietic stem cell regeneration. Nature Genetics https://doi.org/10.1038/s41588-023-01528-2

3. Sarkaria, S.M., Zhou, J., Bao, S., Zhao, W., Fang Y., Que, J., Bhagat G., Zhang C. and Ding, L. (2023) Systematic dissection of coordinated stromal remodeling identified Sox10+ glial cells a therapeutic target in myelofibrosis. Cell Stem Cell 30: 832.

4. Zhang, Y., Zhang, W., Zhao, J., Ito, T., Jin, J., Aparicio, A.O., Zhou, J., Guichard, V., Fang, Y., Que, J., Urban, JF Jr., Hanna, J.H., Ghosh, S., Wu, X., Ding, L., Basu, U. and Huang, Y. (2023) m6A RNA modification regulates innate lymphoid cell responses in a lineage-specific manner. Nature Immunology 24: 1256.

5. Zhu, Q., Ding, L. and Yue, R. (2022) Skeletal stem cells: a game changer of skeletal biology and regenerative medicine? Life Medicine 1: 294.

6. Lee, Y., DiMaulo-Milk, E., Leslie, J. and Ding L. (2022) Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver. Science Advances 8: eabm7688.

7. Lee, Y., Leslie, J., Yang, Y. and Ding, L. (2021) Hepatic stellate and endothelial cells maintain hematopoietic stem cells in the developing liver. Journal of Experimental Medicine 218: e20200882.

8. Gao, L., Decker, M., Chen, H and Ding, L. (2021) Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation. eLife 10: e69894.

9. Lee, Y. and Ding, L. (2021) A polarized anchor for hematopoietic stem cells: Synapse between stem cells and their niche? Journal of Cell Biology 220: e202108031.

10. Nair, L., Zhang, W., Laffleur, B., Jha, M.K., Lim, J., Lee, H., Wu, L., Alvarez, N.S., Liu, Z.P., Munteanu, E.L., Swayne, T., Hanna, J.H., Ding, L., Rothschild, G. and Basu U. (2021) Mechanism of noncoding RNA-associated N6-methyladenosine recognition by an RNA processing complex during IgH DNA recombination. Molecular Cell 81: 3949.

11. Lee, H., Bao, S., Qian, Y., Geula, S., Leslie, J., Zhang, C., Hanna, J. and Ding, L. (2019) Stage-specific requirement for Mettl3-dependent m6A mRNA methylation during haematopoietic stem cell differentiation. Nature Cell Biology 21: 700-709.

12. 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.

13. 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.

14. 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 40doi: 10.1002/bies.201700190. Epub 2018 Jan 31.

15. 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.

16. 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.

17. 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.

18. 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.

19. Ding, L. (2017) HSC niche: ample room for every guest stem cell. Blood 129: 2042-2043. 

20. 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.

21. 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.

22. 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)

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. Ding, L., Saunders, T., Enikolopov, G. and Morrison, S. (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481: 457-462

29. Ding, L. and Han, M. (2007) GW182 family proteins are critical for miRNA-mediated gene silencing. Trends in Cell Biology 17: 411-416.

30. 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)

31. 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.