One stem cell program to rule them all?

Abstract

Many species of animals have stem cells that they maintain throughout their lives, which suggests that stem cells are an ancestral feature of all animals. From this, we take the viewpoint that cells with the biological properties of 'stemness'-self-renewal and multipotency-may share ancestral genetic circuitry. However, in practice is it very difficult to identify and compare stemness gene signatures across diverse animals and large evolutionary distances? First, it is critical to experimentally demonstrate self-renewal and potency. Second, genomic methods must be used to determine specific gene expression in stem cell types compared with non-stem cell types to determine stem cell gene enrichment. Third, gene homology must be mapped between diverse animals across large evolutionary distances. Finally, conserved genes that fulfill these criteria must be tested for role in stem cell function. It is our viewpoint that by comparing stem cell-specific gene signatures across evolution, ancestral programs of stemness can be uncovered, and ultimately, the dysregulation of stemness programs drives the state of cancer stem cells.

Comprehensive comparison of gene expression diversity among a variety of human stem cells

“…HSCs were divided into C7 ( n = 19) and C8 ( n = 4). As expected, pluripotent stem cell clusters (C1 and C2) and somatic stem cell clusters (C3–C8) were separated, coinciding with previous reports on their remarkable differences in the proliferation time and the differentiation potential ( 85 , 86 ). The correspondence between individual stem cells among replicates was also confirmed ( Supplementary Table S1 ).…”

The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

“…However, CSCs exhibit enhanced stemness, often demonstrated molecularly by dysregulation of stem-associated pathways (Malta et al, 2018;Pinto et al, 2015) or functionally by increased self-renewal and potency (O'Brien et al, 2010). Because of this enhanced stemness, the gene expression in pure CSCs can be compared with normal ASCs, with the prediction that genes driving an enhanced stemlike state will have higher expression and their proteins will be more active (Wiggans and Pearson, 2020).…”

“…In order to perform such a comparison, one needs gene expression data from pure stem cells, prior knowledge that a given cell population possesses stemness properties, the genomic resources to compare gene homologs across diverse species, and, perhaps most important, the ability to test gene function in ASCs in vivo. A model system that fulfills these criteria is the freshwater planarian, Schmidtea mediterranea, a flatworm from the phylum Platyhelminthes (Wiggans and Pearson, 2020).…”

A pan‐metazoan concept for adult stem cells: the wobbling Penrose landscape

“…3 and Table S2 . However, it is challenging to identify or compare stemness gene signatures across diverse taxa separated by wide evolutionary distances (Alié et al ., 2015 ; Wiggans & Pearson, 2021 ). Also, the molecular mechanisms by which invertebrates maintain viable ASC stocks, with long‐term stability and constant proliferation during their lifespan, remain elusive (Conte et al ., 2009 ).…”

“…The prevailing vertebrate‐centric paradigm suggests the existence of idiosyncratic populations of adult stem cells (ASCs) in animals (Raff, 2003 ; Wagers & Weissman, 2004 ; Clevers, 2015 ; Wiggans & Pearson, 2021 ). In vertebrates, ASCs are defined as lineage‐restricted with tissue or organ‐specific activities, and are capable of regulating homeostasis, repair and regeneration of tissues and organs (Clevers & Watt, 2018 ).…”