Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke

Abstract

The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK.

Keywords: cancer; competition; leukaemia; neoplasm; stem cell.

Figure 1.

Life cycle of Botryllus schlosseri. B. schlosseri undergoes both sexual and asexual (budding) reproduction, resulting in virtually identical adult body plans. The chordate tadpole, which results from sexual reproduction, settles on a subtidal surface and metamorphoses into an invertebrate founder individual, an oozoid. The oozoid reproduces asexually via budding (through four stages (A–D)) resulting in a colony (left) of genetically identical individuals (blastozooids, also known as zooids). Budding continues throughout the colony's life, producing multiple individuals (buds that grow into zooids every week). Individuals in the colony have anatomical structures including atrial and oral siphons, intestines, a simple tube-like heart and a branchial sac. Connecting the individuals is a network of blood vessels embedded within a gelatinous matrix (termed ‘tunic’); these terminate in finger-like protrusions (ampullae). Adapted from [15]. (Online version in colour.)

Figure 2.

Haematopoietic lineage tree. Schematic of cells at successive differentiation stages with distinctive immunophenotypes (marker profiles) in mouse and human. The haematopoietic stem cell (HSC) is capable of self-renewal and long-term reconstitution of the entire haematopoietic system; the multipotent progenitors are capable of minimal or no self-renewal, resulting in transient reconstitution of multiple lineages. CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte/erythroid progenitor; GMP, granulocyte/macrophage progenitor; MkP, megakaryocyte progenitor; EP, erythroid progenitor; GP, granulocyte progenitor; MacP, macrophage progenitor; Pro-DC, dendritic cell progenitor; Pro-B, B lymphocyte progenitor; Pro-T, T lymphocyte progenitor; Pro-NK, natural killer cell progenitor. Adapted from [36]. (Online version in colour.)

Figure 3.

Single-cell analysis determines the sequence of mutations acquired in preleukaemic HSCs in acute myeloid leukaemia. Each row depicts the proposed clonal evolution of leukaemia in each of three patients. Adapted from [59]. (Online version in colour.)

Figure 4.

Human fetal CNS stem cell derived neurosphere cells injected into the brains of aged, plaque-bearing Tg(APP-SW) mice. A micrograph of a left hemisphere section taken seven weeks after injection shows normal appearing neurons in apposition to a plaque (inset). Courtesy of George Carlson, Nobuko Uchida, Ann Tsukamoto-Weissman, and the author. (Online version in colour.)