原创力文档colon stem cell and crypt dynamics exposed by cell lineage reconstruction结肠隐窝干细胞和动态接触的细胞谱系重建.pdfVIP
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colon stem cell and crypt dynamics exposed by cell lineage reconstruction结肠隐窝干细胞和动态接触的细胞谱系重建
Colon Stem Cell and Crypt Dynamics Exposed by Cell
Lineage Reconstruction
1. 2. 3. 2,3 1 2
Yitzhak Reizel , Noa Chapal-Ilani , Rivka Adar , Shalev Itzkovitz , Judith Elbaz , Yosef E. Maruvka ,
2,3 4 1 2,3
Elad Segev , Liran I. Shlush , Nava Dekel , Ehud Shapiro *
1 Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 2 Department of Computer Science and Applied Mathematics, Weizmann Institute
of Science, Rehovot, Israel, 3 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel, 4 Rappaport Faculty of Medicine and Research Institute,
Technion and Rambam Medical Center, Haifa, Israel
Abstract
Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a
retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This
method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell
markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established
facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that,
throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence
of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite
mutations. In addition, we confirmed the positive corre
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