**1. Introduction**

Haematopoiesis, the process of generation of blood cells, is one of the most extensively studied developmental systems. The whole spectrum of blood cells produced in mammalian organ‐ isms includes primitive erythrocytes and definitive haematopoietic cells such as myeloid, lymphoid, definitive erythroid and haematopoietic stem cells (HSCs).

Haematopoiesis takes place in several locations during ontogeny and in adult life. The embryonic origin of blood cells has been studied for more than a century. However, studies on haematopoiesis *in vivo* are challenging as embryos, and in particular mammalian embryos, are extremely small and difficult to access at these very early stages of development. Moreover, the number of cells per embryo is limited and all the successive developmental events take place very fast. Therefore different approaches have been developed to facilitate these studies *in vitro* and one of them involves the use of embryonic stem (ES) cell *in vitro* differentiation. In this chapter, we will highlight some recent results on studies of the development of the haematopoietic system obtained in particular using the *in vitro* differentiation of murine ES cells. We will also present the methods we routinely use in our laboratory to work with wild type or genetically modified murine ES cells.

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