RESUMEN
Two types of stem cells are currently defined in small intestinal crypts: cycling crypt base columnar (CBC) cells and quiescent '+4' cells. Here, we combine transcriptomics with proteomics to define a definitive molecular signature for Lgr5(+) CBC cells. Transcriptional profiling of FACS-sorted Lgr5(+) stem cells and their daughters using two microarray platforms revealed an mRNA stem cell signature of 384 unique genes. Quantitative mass spectrometry on the same cell populations identified 278 proteins enriched in intestinal stem cells. The mRNA and protein data sets showed a high level of correlation and a combined signature of 510 stem cell-enriched genes was defined. Spatial expression patterns were further characterized by mRNA in-situ hybridization, revealing that approximately half of the genes were expressed in a gradient with highest levels at the crypt bottom, while the other half was expressed uniquely in Lgr5(+)stem cells. Lineage tracing using a newly established knock-in mouse for one of the signature genes, Smoc2, confirmed its stem cell specificity. Using this resource, we find-and confirm by independent approaches-that the proposed quiescent/'+4' stem cell markers Bmi1, Tert, Hopx and Lrig1 are robustly expressed in CBC cells.
Asunto(s)
Antígenos de Diferenciación/metabolismo , Regulación de la Expresión Génica , Mucosa Intestinal/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Madre/metabolismo , Animales , Antígenos de Diferenciación/genética , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Perfilación de la Expresión Génica , Intestinos/citología , Ratones , Ratones Transgénicos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptores Acoplados a Proteínas G/genética , Células Madre/citologíaRESUMEN
Home-work commuting has always attracted significant research attention because of its impact on human mobility. One of the key assumptions in this domain of study is the universal uniformity of commute times. However, a true comparison of commute patterns has often been hindered by the intrinsic differences in data collection methods, which make observation from different countries potentially biased and unreliable. In the present work, we approach this problem through the use of mobile phone call detail records (CDRs), which offers a consistent method for investigating mobility patterns in wholly different parts of the world. We apply our analysis to a broad range of datasets, at both the country (Portugal, Ivory Coast, and Saudi Arabia), and city (Boston) scale. Additionally, we compare these results with those obtained from vehicle GPS traces in Milan. While different regions have some unique commute time characteristics, we show that the home-work time distributions and average values within a single region are indeed largely independent of commute distance or country (Portugal, Ivory Coast, and Boston)-despite substantial spatial and infrastructural differences. Furthermore, our comparative analysis demonstrates that such distance-independence holds true only if we consider multimodal commute behaviors-as consistent with previous studies. In car-only (Milan GPS traces) and car-heavy (Saudi Arabia) commute datasets, we see that commute time is indeed influenced by commute distance. Finally, we put forth a testable hypothesis and suggest ways for future work to make more accurate and generalizable statements about human commute behaviors.