Credentials: PhD, Molecular Genetics
Position title: Assistant Professor, Cell and Regenerative Biology
- Organ System/Disease Focus
- Hematopoietic stem cells, Stem cell niche
- Aligned Research Focus
- Hematopoietic stem cell development in mouse and zebrafish, live imaging of hematopoietic stem cells
We use multiple approaches and model organisms to understand the fundamental biology that regulates hematopoietic stem cells (HSCs) in their niche. Harnessing the strength of each model, we are building a dynamic view of stem cell behavior in relation to multiple niche cell types. HSCs are concurrently regulated by many different cell types, including endothelial and mesenchymal stromal cells, as well as other hematopoietic cells. The hematopoietic system is very highly conserved so data from mouse and zebrafish often translates to humans.
We use zebrafish because they are a well-characterized functional genetic model with endogenous labels that allow direct live imaging of the endogenous niche. This allows us to test novel hypotheses that could not be performed in any other model system. The high efficiency of CRISPR/Cas9 gene editing in zebrafish now allows the rapid generation of mutant models. Together with transgenic fluorescent reporters of hematopoietic stem cells and many niche cell types, we can track live cellular interactions in wild-type and mutant genetic backgrounds. We are using correlative light and electron microscopy (CLEM) to look at the ultrastructure of endogenous HSCs in their niche.
We use mouse as an established HSC transplant model with an extensive panel of markers that can be used to dissect in fine detail changes within the hematopoietic system. We are currently focused on neurotransmitters that are found in the bone marrow niche, and neuroreceptors that are expressed on HSCs themselves. We are finding fascinating novel regulatory mechanisms that have the potential to improve clinical HSC transplantations.
Sample of Stem Cell Specific References
1. *Tamplin OJ, *Durand EM, Carr LA, Childs SJ, Hagedorn EJ, Li P, Yzaguirre AD, Speck NA, Zon LI. Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche. Cell. 2015;160(1-2):241-52. Epub 2015/01/17. doi: 10.1016/j.cell.2014.12.032. PubMed PMID: 25594182; PMCID: PMC4346256.
2. Jing L, Tamplin OJ, Chen MJ, Deng Q, Patterson S, Kim PG, Durand EM, McNeil A, Green JM, Matsuura S, Ablain J, Brandt MK, Schlaeger TM, Huttenlocher A, Daley GQ, Ravid K, Zon LI. Adenosine signaling promotes hematopoietic stem and progenitor cell emergence. J Exp Med. 2015;212(5):649-63. Epub 2015/04/15. doi: 10.1084/jem.20141528. PubMed PMID: 25870200; PMCID: PMC4419349.
3. *Li P, *Lahvic JL, *Binder V, Pugach EK, Riley EB, Tamplin OJ, Panigrahy D, Bowman TV, Barrett FG, Heffner GC, McKinney-Freeman S, Schlaeger TM, Daley GQ, Zeldin DC, Zon LI. Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature. 2015;523(7561):468-71. Epub 2015/07/24. doi: 10.1038/nature14569. PubMed PMID: 26201599.
4. Blaser BW, Moore JL, Hagedorn EJ, Li B, Riquelme R, Lichtig A, Yang S, Zhou Y, Tamplin OJ, Binder V, Zon LI. CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment. J Exp Med. 2017;214(4):1011-27. doi: 10.1084/jem.20161616. PubMed PMID: 28351983; PMCID: PMC5379982.
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