Universality of clone dynamics during tissue development.

The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes. By mapping clonal dynamics onto a generalization of the classical theory of aerosols, we elucidate the origin and range of scaling behaviours and show how the identification of universal scaling dependences may allow lineage-specific information to be distilled from experiments. Our study shows the emergence of core concepts of statistical physics in an unexpected context, identifying cellular systems as a laboratory to study non-equilibrium statistical physics.Wellcome Trus

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.Wellcome Trus

Controlled whole body vibration to decrease fall risk and improve health-related quality of life of nursing home residents

Objective: To investigate the effects of whole body vibration in the elderly. Design: Randomized controlled trial. Setting: Nursing home. Participants: Forty-two elderly volunteers. Interventions: Six-week vibration intervention plus physical therapy (PT) (n=22) or PT alone (n=20). Main Outcome Measures: We assessed gait and body balance using the Tinetti test (maximum scores of 12 for gait, 16 for body balance, 28 for global score), motor capacity using the Timed Up & Go (TUG) test, and health-related quality of life (HRQOL) using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Results: After 6 weeks, the vibration intervention group improved by a mean +/- standard deviation of 2.4 +/- 2.3 points on the gait score compared with no score change in the control group (P<.001). The intervention group improved by 3.5 +/- 2.1 points on the body balance score compared with a decrease of 03 +/- 1.2 points in the control group (P<.001). TUG test time decreased by 11.0 +/- 8.6 seconds in the treated group compared with an increase of 2.6 +/- 8.8 seconds in the control group (P<.001). The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group. Conclusions: Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients

Controlled whole body vibration to decrease fall risk and improve health related quality of life in elderly patients

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Early lineage segregation of multipotent embryonic mammary gland progenitors.

The mammary gland is composed of basal cells and luminal cells. It is generally believed that the mammary gland arises from embryonic multipotent progenitors, but it remains unclear when lineage restriction occurs and what mechanisms are responsible for the switch from multipotency to unipotency during its morphogenesis. Here, we perform multicolour lineage tracing and assess the fate of single progenitors, and demonstrate the existence of a developmental switch from multipotency to unipotency during embryonic mammary gland development. Molecular profiling and single cell RNA-seq revealed that embryonic multipotent progenitors express a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in embryonic multipotent progenitors promotes unipotent basal cell fate and was sufficient to reprogram adult luminal cells into basal cells by promoting an intermediate hybrid multipotent-like state. Altogether, this study identifies the timing and the mechanisms mediating early lineage segregation of multipotent progenitors during mammary gland development.SCOPUS: ar.jSCOPUS: er.jinfo:eu-repo/semantics/publishe