A cytological study of the capacity for differentiation of normal hemopoietic colony‐forming cells

Abstract

A two-stage procedure has been used to obtain hemopoietic spleen colonies derived from single precursor cells containing radiation-induced chromosomal markers. Of a total of 46 colonies examined, 17 were found to contain cells with abnormal karyotypes. In each of the 17 marked colonies, 90% or more of the dividing cells in the colony carried the same marker. Cell suspensions prepared from each of the individual colonies were tested for their content of dividing cells possessing recognizable differentiated functions. Metaphase cells with peroxidase-positive granules in their cytoplasm were considered to be members of the granulopoietic series, while metaphase cells which contained Fe5j were considered to be members of the erythropoietic series. Results were obtained for 12 of the marked colonies, and in nine of these, the percentage of metaphases lacking the marker was less than the percentage of metaphases which were scored as erythropoietic, and also was less than the percentage of metaphases scored as granulopoietic. This i s the result which would be expected if the marker were present in both erythropoietic and granulopoietic cells. These results provide support for the view that colony forming hemopoietic stem cells are multipotent, and that differentiation along more than one pathway can occur during the formation of macroscopic splenic colonies.

Induction of T-Cell Differentiation In Vitro by Thymin, a Purified Polypeptide Hormone of the Thymus

“…The finding that 5-10% of bone marrow cells were induced to differentiate by extremely low concentrations of pure thymin suggested that these cells were stem cells with appropriate receptors, and thus already committed to eventual thymocyte differentiation. This large population of committed cells would be distinct from the totipotent hematopoietic stem cells, which make up less than 0.1% of the cells in the murine bone marrow (22). Using crude thymus extracts, Komuro and Boyse (8) also demonstrated this large population of mouse hematopoietic cells susceptible to differentiation by a thymus-inducing factor.…”

Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation

“…Animals were killed on days 1 to 4,8,12,16, and 20 after irradiation for histologic analyses. Morphologic analysis of whole animal sections stained with hematoxylin and eosin over 0 Gy to 45 Gy showed an apparent threshold dose of 20 Gy that specifically ablated the majority of cells within hematopoietic tissues.…”

“…Although humoral factors produced from these tissues were initially proposed to be the radioprotective elements, 2 subsequent studies showed that survival correlated with the level of hematopoietic repopulation by donor-derived cells. [5][6][7][8] Pioneering studies by Till and McCulloch and colleagues showed that donor bone marrow contained rare cells that generated clonal, macroscopic spleen colonies, 9,10 a fraction of which regenerated spleen colonies 11 or repopulated multilineage hematopoiesis 12 in hosts receiving serial transplants. These experiments led to the concept of the hematopoietic stem cell (HSC).…”

Antigenic Differences Between Hemopoietic Stem Cells and Myeloid Progenitors

“…(Received for publication 5 March 1974) There is general agreement that the mature cells of the blood of mammals arise from a pluripotent hemopoietic stem cell (1)(2)(3)(4). This cell is defined by ability to form spleen colonies after injection into lethally irradiated mice (5) and is thus called a spleen colony-forming unit or CFU-s. Colonies of myeloid cells can be formed in vitro (6,3) and the cells which give rise to these colonies (CFU-c) differ in many properties from the CFU-s.…”

“…This cell is defined by ability to form spleen colonies after injection into lethally irradiated mice (5) and is thus called a spleen colony-forming unit or CFU-s. Colonies of myeloid cells can be formed in vitro (6,3) and the cells which give rise to these colonies (CFU-c) differ in many properties from the CFU-s. The CFU-c appear to be slightly denser (8,9), have a higher sedimentation rate, (8) and have a larger proportion of cells in S phase of the cell cycle than CFU-s (10,11).…”