title: Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.
abstract: In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry), where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry), where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.
authors.affiliation: Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Yun-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Greenberg
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Wu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhai
mesh_terms: D000367:Age Factors; D000818:Animals; D060049:Asymmetric Cell Division; D002454:Cell Differentiation; D049109:Cell Proliferation; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000502:physiology; D051379:Mice; D008962:Models, Theoretical; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism