The Imaging Core of the Yale Center of Excellence in Hematology promotes the use of imaging technology in hematology and makes a large array of imaging platforms readily accessible to investigators with a research interest in hematopoiesis, locally or nationally.
Yale is the home of many cutting-edge pieces of imaging equipment and associated facilities but identifying the one suitable for your needs can be a challenge. We are here to consult with you on your imaging needs and to help you identify which microscopy technique is the most useful or promising one to address your research question.
We are closely associated with state-of-the-art imaging facilities:
- CCMI– confocal microscopy, 2-photon microscopy, STED super-resolution microscopy
- CINEMA– spinning disk microscopy, TIRF microscopy, structured illumination super-resolution microscopy
- FACS Facility– Imaging Flow Cytometer among other techniques
- In vivo Imaging Facility– 2-photon microscopy
We also provide access to several research lab-based equipment and techniques and offer training and support for these:
- STED and single-molecule switching (FPALM/PALM/STORM) super-resolution microscopy
- Automated long-term live-cell imaging
- Tissue clearing
Hematopoiesis starts from hematopoietic stem cells. Through self-renewal and differentiation, they give rise to all cell types in the blood. Many important questions regarding key steps in hematopoiesis have benefited greatly from imaging techniques. A few examples are provided below. We believe imaging could help solve many more questions regarding hematopoiesis. If you are thinking of employing imaging as a tool in your hematopoietic studies but are uncertain about how to start, please contact us.
Question 1: Before “self-renewal”, where do the first hematopoietic stem cells come from? These papers directly visualized the emergence of hematopoietic cells from the endothelial lineage, providing direct evidence for the developmental origin of hematopoietic cells.
Continuous single-cell imaging of blood generation from haemogenic endothelium.
Eilken HM, Nishikawa S, Schroeder T.
Nature. 2009 Feb 12;457(7231):896-900. doi: 10.1038/nature07760.
Haematopoietic stem cells derive directly from aortic endothelium during development.
Bertrand JY, Chi NC, Santoso B, Teng S, Stainier DY, Traver D.
Nature. 2010 Mar 4;464(7285):108-11. doi: 10.1038/nature08738. Epub 2010 Feb 14.
In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium.
Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C.
Nature. 2010 Mar 4;464(7285):116-20. doi: 10.1038/nature08764. Epub 2010 Feb 14.
Question 2: Hematopoietic stem cells are extremely rare. Each animal possesses ~104-105 of such cells. Where do these rare cells reside in vivo? These papers visualize deep into the bone marrow, giving us the glimpse of what the niche might look like.
Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche.
Lo Celso C, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, Côté D, Rowe DW, Lin CP, Scadden DT.
Nature. 2009 Jan 1;457(7225):92-6.
Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal.
Acar M, Kocherlakota KS, Murphy MM, Peyer JG, Oguro H, Inra CN, Jaiyeola C, Zhao Z, Luby-Phelps K, Morrison SJ.
Nature. 2015 Oct 1;526(7571):126-30.
Arteriolar niches maintain haematopoietic stem cell quiescence.
Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS.
Nature. 2013 Oct 31;502(7473):637-43.
Multimodal imaging reveals structural and functional heterogeneity in different bone marrow compartments: functional implications on hematopoietic stem cells.
Lassailly F, Foster K, Lopez-Onieva L, Currie E, Bonnet D.
Blood. 2013 Sep 5;122(10):1730-40.
Question 3: For a multipotent hematopoietic progenitor, how does it determine which lineage to differentiate into, such as when deciding the lymphoid versus the myeloid fate choice? These papers followed single hematopoietic progenitors and their clonal growth to determine when and how cell identity is acquired.
M-CSF instructs myeloid lineage fate in single haematopoietic stem cells.
Mossadegh-Keller N, Sarrazin S, Kandalla PK, Espinosa L, Stanley ER, Nutt SL, Moore J, Sieweke MH.
Nature. 2013 May 9;497(7448):239-43.
Positive feedback between PU.1 and the cell cycle controls myeloid differentiation.
Kueh HY, Champhekar A, Nutt SL, Elowitz MB, Rothenberg EV.
Science. 2013 Aug 9;341(6146):670-3.
The above papers are intended to serve as examples for how imaging has helped to define our knowledge about several key steps in hematopoiesis. Many more papers are not listed here, and many more questions are waiting to be addressed. We encourage you to consider imaging as one the tools even if you have not used it extensively before. Please let us know how we can help you to get started!
Please contact us to arrange a meeting and go over your needs and explore the available options.