The critical role of the nucleolus in cell differentiation and stem cell development — The concept as it applies to the malignant cell

A new approach to cell staining and cell culture is used which allows for better observation of nucleolar behaviour than is possible with traditional methods. The role of the nucleolus in stem cell maturation in the mosquito and woodlouse is discussed, and evidence presented to show that certain of their stem cells are multi-nucleolated cells and that they give rise to a clone of small round cells (daughter cells) by a novel method of division. This type of cell formation has been given the name “clonal division” to distinguish it from classical mitotic division. The new approach is used in the search for the elusive haemopoietic stem cell and evidence presented to show that this is also a multinucleolated stem cell which, in like fashion, gives rise to a clone of small round cells. The development takes place extravascularly, and the small round cells which arise are the immediate precursors of the differentiated cells found in peripheral blood. An analysis of the role of the nucleolus in stem cell development is made, and the conclusion reached that it plays an important part in clonal division, its behaviour being consistent with some form of instructional role. It is suggested that all primitive cells are enveloped in a basophilic reticulum which is composed of instructional RNA responsible for the transformation of the primitive cell into a differentiated cell. It is further suggested that the nucleoli and basophilic reticulum are but interchangeable forms of the one structure (to be known as nucleolar material), and that this is inherited the same way that chromosomal material is inherited.