Identifying the Differentiation Stages of Individual Hematopoietic Cells by Multivariate Analysis of Secondary Ion Mass Spectra

Identification of the mechanical and biochemical properties that induce hematopoietic stem cells (HSCs) to self-renew or differentiate into various types of blood and immune cells is an important goal in tissue engineering. Combinatorial biomaterial substrates permit screening the effects of multiple microenvironments on stem cell fate while using a minimum number of cells. To utilize these substrates, robust and quantitative methods to identify the differentiation stages of individual cells with location specificity are required.  For this purpose, we have used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to collect spectra that encodes for the surface chemistries of individual cells from distinct hematopoietic cell populations.  We then used a multivariate analysis technique, partial least-squares-discriminant analysis (PLS-DA) to construct a PLS-DA model that could be used to identify the differentiation stages of individual hematopoietic cells that were isolated from mouse bone marrow according to their mass spectra. This approach may facilitate correlating HSC fates with the properties that control them.