Metakaryotic stem cell lineages in organogenesis of humans and other metazoans

Abstract

A non-eukaryotic, metakaryotic cell with large, open mouthed, bell shaped nuclei represents an important stem cell lineage in fetal/juvenile organogenesis in humans and rodents. each human bell shaped nucleus contains the diploid human DNA genome as tested by quantitative Feulgen DNA cytometry and fluorescent in situ hybridization with human pan-telomeric, pan-centromeric and chromosome specific probes. From weeks approximately 5-12 of human gestation the bell shaped nuclei are found in organ anlagen enclosed in sarcomeric tubular syncytia. Within syncytia bell shaped nuclear number increases binomially up to 16 or 32 nuclei; clusters of syncytia are regularly dispersed in organ anlagen. Syncytial bell shaped nuclei demonstrate two forms of symmetrical amitoses, facing or "kissing" bells and "stacking" bells resembling separation of two paper cups. Remarkably, DNA increase and nuclear fission occur coordinately. Importantly, syncytial bell shaped nuclei undergo asymmetrical amitoses creating organ specific ensembles of up to eight distinct closed nuclear forms, a characteristic required of a stem cell lineage. Closed nuclei emerging from bell shaped nuclei are eukaryotic as demonstrated by their subsequent increases by extra-syncytial mitoses populating the parenchyma of growing anlagen. From 9-14 weeks syncytia fragment forming single cells with bell shaped nuclei that continue to display both symmetrical and asymmetrical amitoses. These forms persist in the juvenile period and are specifically observed in bases of colonic crypts. Metakaryotic forms are found in organogenesis of humans, rats, mice and the plant Arabidopsis indicating an evolutionary origin prior to the divergence of plants and animals.

Human fetal/tumor metakaryotic stem cells: pangenomic homologous pairing and telomeric end-joining of chromatids

“…Anonymous surgical discards were fixed immediately upon surgical removal in Carnoy’s solution and stored under refrigeration in 70% ethanol [1, 3]. Fetal tissues of hindgut (5–7 wks gestation) and of spinal cord (9 –10 wks) were used for the cytometric analyses reported here.…”

“…The resulting macerated sample was twice spun down and washed in distilled water and then applied to slides for spreading [3]. …”

“…Feulgen DNA image cytometry reveals that bell shaped nuclei increase by either of two forms of symmetrical amitoses concomitant with DNA doubling without chromosomal condensation. Furthermore, cells with bell-shaped nuclei undergo asymmetric amitoses to create a diverse set of cells with at least nine distinguishable nuclear morphotypes including those of the fetal and tumor parenchymal cells that subsequently increased in number by mitoses [1, 2, 3]. …”

“…The cytological evidence of asymmetric nuclear fissions creating specific nuclear morphotypes of cells that subsequently divide by mitosis and comprise the fetal/juvenile tissue or tumor parenchyma supports the hypothesis that cells with bell shaped nuclei comprise a stem cell lineage in organogenesis and carcinogenesis. The metakaryotic stem cell lineage is observed in fetal tissues derived from all three primordial layers of the human embryonic blastula: ectoderm, mesoderm and ectoderm [3]. Nearly identical metakaryotic forms populate fetal mouse and rat tissues as well as the developing plant Arabidopsis suggesting an evolutionary origin prior to the separation of plants and animals [3].…”

“…The metakaryotic stem cell lineage is observed in fetal tissues derived from all three primordial layers of the human embryonic blastula: ectoderm, mesoderm and ectoderm [3]. Nearly identical metakaryotic forms populate fetal mouse and rat tissues as well as the developing plant Arabidopsis suggesting an evolutionary origin prior to the separation of plants and animals [3]. The distribution of the number of point mutant colonies as a function of size in adult human lungs indicates that the stem cell lineage of fetal/juvenile growth and development is mutator or hypermutable in phenotype and that maintenance stem cells of adult tissues have much lower mutation rates [4].…”