No abstract; Selected excerpts
Cellular senescence (or senescence) has been regarded as a stable form of cell cycle arrest by in vitro cell culture experiments.1 Recent studies indicate that senescence is associated with aging and diseases, including cancers.2,3 For instances, it suppresses tumor progression by halting the growth of premalignant cells,4 and promotes wound healing by preventing excessive tissue fibrosis or induction of cell dedifferentiation.5,6 Targeting senescent cells could restore tissue homeostasis in response to aging, chemotoxicity, or injury.7 In addition to these pathological conditions in adults, cellular senescence also occurs in physiological states such as mammalian mouse8,9 and human10,11 embryonic development. Embryonic senescent cells have been reported to be non-proliferative and subjected to clearance from tissues after apoptosis at late embryonic stage.8,9 However, the interpretation for clearance of senescent cells at late embryonic stage is based on the disappearance of Cdkn1a (P21) expression and senescence-associated beta-galactosidase (SAβ-Gal) activity,8,9 two commonly used senescence markers in the field. Currently, there is no genetic fate mapping evidence for senescent cell fate in vivo. By lineage tracing of P21+ senescent cells, we found that embryonic senescent cells labeled at mid-embryonic stage gradually lost P21 expression and SAβ-Gal activity at late embryonic stage. Unexpectedly, some of the previously labeled senescent cells re-entered the cell cycle and proliferated in situ. Moreover, these previously labeled senescent cells were not cleared at late embryonic stage and remained in the tissue after birth. This study unravels in vivo senescent cell fates during embryogenesis, indicating their potential plasticity.
Erratum in
* Author Correction: Embryonic senescent cells re-enter cell cycle and contribute to tissues after birth. [Cell Res. 2018]