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Skeletal progenitor/stem cells (SSCs) play a critical role in postnatal bone growth and maintenance. Telomerase (Tert) activity prevents cellular senescence and is required for maintenance of stem cells in self‐renewing tissues. Here we investigated the role of mTert‐expressing cells in postnatal mouse long bone and found that mTert expression is enriched at the time of adolescent bone growth. mTert‐GFP+ cells were identified in regions known to house SSCs, including the metaphyseal stroma, growth plate, and the bone marrow. We also show that mTert‐expressing cells are a distinct SSC population with enriched colony‐forming capacity and contribute to multiple mesenchymal lineages, in vitro. In contrast, in vivo lineage‐tracing studies identified mTert + cells as osteochondral progenitors and contribute to the bone‐forming cell pool during endochondral bone growth with a subset persisting into adulthood. Taken together, our results show that mTert expression is temporally regulated and marks SSCs during a discrete phase of transitional growth between rapid bone growth and maintenance., In long bones, osteochondral progenitor cells function during rapid bone growth while osteoadipogenic progenitors act during bone maintenance. We showed that mTert is expressed in an age‐dependent manner and marks growth‐associated osteochondral progenitor cells during transitional growth, a discrete time period between rapid bone growth and bone maintenance.

SummaryThe cellular and molecular mechanisms underlying adaptive changes to physiological stress within the intestinal epithelium remain poorly understood. Here, we show that PTEN, a negative regulator of the PI3K→AKT→mTORC1-signaling pathway, is an important regulator of dormant intestinal stem cells (d-ISCs). Acute nutrient deprivation leads to transient PTEN phosphorylation within d-ISCs and a corresponding increase in their number. This release of PTEN inhibition renders d-ISCs functionally poised to contribute to the regenerative response during re-feeding via cell-autonomous activation of the PI3K→AKT→mTORC1 pathway. Consistent with its role in mediating cell survival, PTEN is required for d-ISC maintenance at baseline, and intestines lacking PTEN have diminished regenerative capacity after irradiation. Our results highlight a PTEN-dependent mechanism for d-ISC maintenance and further demonstrate the role of d-ISCs in the intestinal response to stress.

The intestinal epithelium is maintained by a population of rapidly cycling ( Lgr5 + ) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase ( mTert ) expression that can give rise to Lgr5 + cells. mTert -expressing cells distribute in a pattern along the crypt–villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert + cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.