What is the role of PIWI family proteins in adult pluripotent stem cells? Insights from asexually reproducing animals, planarians

2020 ◽  
Vol 62 (6) ◽  
pp. 407-422
Author(s):  
Makoto Kashima ◽  
Kiyokazu Agata ◽  
Norito Shibata
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Adult Pluripotent Stem Cells

scholarly journals OncogenicPIK3CApromotes cellular stemness in an allele dose-dependent manner

2019 ◽  
Vol 116 (17) ◽  
pp. 8380-8389 ◽  
Author(s):  
Ralitsa R. Madsen ◽  
Rachel G. Knox ◽  
Wayne Pearce ◽  
Saioa Lopez ◽  
Betania Mahler-Araujo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Dependent Manner ◽  
Developmental Context ◽  
Epithelial Morphology ◽  
Pi3k Signaling Pathway ◽  
Induced Pluripotent

ThePIK3CAgene, which encodes the p110α catalytic subunit of PI3 kinase (PI3K), is mutationally activated in cancer and in overgrowth disorders known asPIK3CA-related overgrowth spectrum (PROS). To determine the consequences of geneticPIK3CAactivation in a developmental context of relevance to both PROS and cancer, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous knockin ofPIK3CAH1047R. While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity forPIK3CAH1047Rcaused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. Genetic analysis ofPIK3CA-associated cancers revealed that 64% had multiple oncogenicPIK3CAcopies (39%) or additional PI3K signaling pathway-activating “hits” (25%). This contrasts with the prevailing view thatPIK3CAmutations occur heterozygously in cancer. Our findings suggest that a PI3K activity threshold determines pathological consequences of oncogenicPIK3CAactivation and provide insight into the specific role of this pathway in human pluripotent stem cells.

Flatworm asexual multiplication implicates stem cells and regeneration

2004 ◽  
Vol 82 (2) ◽  
pp. 334-356 ◽  
Author(s):  
Maria Reuter ◽  
Natalia Kreshchenko
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Early Stage ◽  
Gradient System ◽  
Decisive Importance ◽  
Present Information ◽  
Asexual Multiplication ◽  
Primitive Feature ◽  
Head Regeneration

The phenomenon of asexual multiplication is rare in the animal kingdom, but it occurs in all main flatworm taxa. In the present paper, we review data regarding the presence of different forms of asexual multiplication in flatworms and argue that the presence of a population of totipotent or pluripotent stem cells, "neoblasts", is a primitive feature of decisive importance for the developing potential of flatworms. Next we present information on the role of stem cells in fission, head regeneration, and pharynx regeneration of planarians. Furthermore, the tracing of neoblasts in lower flatworms and cestodes is presented, and the results indicating heterogeneity of the neoblast pool are discussed. Finally, the mode by which the neoblasts are stimulated to divide, migrate, and differentiate and the nature of the interactions are discussed. We focus on (i) biogenic amines and neuropeptides, (ii) the role of neuropeptides in the early stage of regeneration, (iii) the evidence for the influences of growth factors and nitric oxide, and (iv) the influence of weak electromagnetic fields. We discuss the pattern in which a gradient system of morphogens and (or) a hierarchical system of inductions is expressed in development.

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