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Article

Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells

1
eGenesis, Cambridge, MA 02139, USA
2
Divisions of Oral and Craniofacial Science & Craniofacial and Surgical Care, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA
3
AxoSim, Inc., New Orleans, LA 70112, USA
4
Asymmetrex, LLC, Boston, MA 02130, USA
*
Author to whom correspondence should be addressed.
Symmetry 2020, 12(11), 1868; https://doi.org/10.3390/sym12111868
Received: 14 October 2020 / Revised: 2 November 2020 / Accepted: 11 November 2020 / Published: 13 November 2020
(This article belongs to the Special Issue Left-Right Asymmetry in Cell Biology)
The loss of genetic fidelity in tissue stem cells is considered a significant cause of human aging and carcinogenesis. Many cellular mechanisms are well accepted for limiting mutations caused by replication errors and DNA damage. However, one mechanism, non-random sister chromatid segregation, remains controversial. This atypical pattern of chromosome segregation is restricted to asymmetrically self-renewing cells. Though first confirmed in murine cells, non-random segregation was originally proposed by Cairns as an important genetic fidelity mechanism in human tissues. We investigated human hepatic stem cells expanded by suppression of asymmetric cell kinetics (SACK) for evidence of non-random sister chromatid segregation. Cell kinetics and time-lapse microscopy analyses established that an ex vivo expanded human hepatic stem cell strain possessed SACK agent-suppressible asymmetric cell kinetics. Complementary DNA strand-labeling experiments revealed that cells in hepatic stem cell cultures segregated sister chromatids non-randomly. The number of cells cosegregating sister chromatids with the oldest “immortal DNA strands” was greater under conditions that increased asymmetric self-renewal kinetics. Detection of this mechanism in a human tissue stem cell strain increases support for Cairns’ proposal that non-random sister chromatid segregation operates in human tissue stem cells to limit carcinogenesis. View Full-Text
Keywords: hepatic stem cell; SACK; xanthosine; xanthine; hypoxanthine; asymmetric cell kinetics; chromosome segregation; sister chromatids; non-random segregation; immortal DNA hepatic stem cell; SACK; xanthosine; xanthine; hypoxanthine; asymmetric cell kinetics; chromosome segregation; sister chromatids; non-random segregation; immortal DNA
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MDPI and ACS Style

Panchalingam, K.; Jacox, L.; Cappiello, B.D.; Sherley, J.L. Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells. Symmetry 2020, 12, 1868. https://doi.org/10.3390/sym12111868

AMA Style

Panchalingam K, Jacox L, Cappiello BD, Sherley JL. Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells. Symmetry. 2020; 12(11):1868. https://doi.org/10.3390/sym12111868

Chicago/Turabian Style

Panchalingam, Krishnanchali, Laura Jacox, Benjamin D. Cappiello, and James L. Sherley 2020. "Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells" Symmetry 12, no. 11: 1868. https://doi.org/10.3390/sym12111868

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