Hematopoietic stem cell research has made tremendous progress over the last decades, and blood has become one of the best understood mammalian stem cell systems. The easy accessibility of hematopoietic cells, which are not tightly embedded in tissue, has supported this fast development. However, the hematopoietic system also exhibits disadvantages over other stem cell systems: the identity of individual cells is quickly lost when followed in cell culture and developmental stages cannot easily be distinguished by morphology. Therefore, difficulties to constantly analyze the fate of single cells are one reason for many open questions in hematopoiesis. So far, most findings are based on endpoint analyses of populations, consisting of heterogeneous cells in different stages of development or cell cycle. However, endpoint analyses merely reflect the result of a progressive sequence of fate decisions, whereas individual decisions, which would elucidate stem cell behavior, are not investigated. Thorough observation of the fate of individual cells and their progeny over many generations will add to a comprehensive understanding of the regulation of stem cell behavior. Here, we review current attempts of single cell analyses in hematopoiesis research and outline how time-lapse imaging and single cell tracking can contribute to approaching long-standing questions in hematopoiesis.

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