Yunhua Zhu, Yi-Fu Huang, Calvina Kek and Dmitry V. Bulavin
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
Published in Cell Stem Cell on 14 February 2013.
This article has been recommended by Faculty of 1000
Emerging lineage tracing data support the existence of several pools of intestinal stem cells (ISCs) in the adult mouse. The +4 location is known to harbor proliferative cells undergoing robust apoptosis in response to irradiation, but their relationship with recently reported intestinal stem cell models is unclear. Here, we found that tamoxifen, at doses commonly used to induce lineage tracing, mimics the irradiation-induced apoptotic response of the +4 cells. We found that about 40% of apoptotic cells were Lgr5-positive while Bmi1-positive ISCs became sensitive to tamoxifen upon entering a proliferative state. In turn, when we suppressed apoptosis by either blc2 overexpression or Chk2 deletion we found that lineage tracing of Lgr5-positive cells was efficiently reduced. In contrast, lineage tracing from Bmi1-positive ISCs was substantially increased in apoptosis-deficient backgrounds. We propose that apoptosis plays an important role in controlling lineage tracing from different ISC populations in the mouse intestine.
Tamoxifen induces efficient apoptosis of Lgr5-positive and Lgr5-negative cells in the mouse intestine. Apoptosis was analyzed by TUNEL assay and Lgr5 expression based on expression of GFP. Representative photographs of a TUNEL+ GFP- cell (top) and TUNEL+GFP+ cell (bottom) after injection of tamoxifen are shown.
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