Dataset Information

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.

ABSTRACT: High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level. We find that high altitude vastly affects the blood transcriptome and, unexpectedly, does not necessarily follow a monotonic response to altitude elevation. Importantly, we observe daily variance in gene expression, especially immune-related genes, which is largely altitude dependent. Moreover, using a digital cytometry approach, we estimate relative changes in abundance of different cell types and find that the response of several immune cell types is time- and altitude dependent. Taken together, our data provide evidence for interaction between the transcriptional response to hypoxia and the time of day in humans.

SUBMITTER: Manella G

PROVIDER: S-EPMC9396531 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.

Manella Gal G Ezagouri Saar S Champigneulle Benoit B Gaucher Jonathan J Mendelson Monique M Lemarie Emeline E Stauffer Emeric E Pichon Aurélien A Howe Connor A CA Doutreleau Stéphane S Golik Marina M Verges Samuel S Asher Gad G

Cell reports 20220801 7

High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level. We find that high altitude vas ...[more]

PMID: 35977481

Similar Datasets

Project description:IntroductionChronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude.MethodsMen aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude.ResultsNinety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= -0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders.ConclusionsLower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.

Project description:ObjectiveTo illuminate the key components of multi-sector reform to address the obesogenic environment in New York City during the administration of Mayor Michael Bloomberg from 2002 to 2013, we conducted a case study consisting of interviews with and a critical analysis of the experiences of leading decision makers and implementers.MethodKey informant interviews (N = 41) conducted in 2014 were recorded, transcribed, coded, and thematically analyzed. Participants included officials from the Health Department and other New York City Government agencies, academics, civil society members, and private sector executives.ResultsParticipants described Mayor Bloomberg as a data-driven politician who wanted to improve the lives of New Yorkers. He appointed talented Commissioners and encouraged them and their staff to be bold, innovative, and collaborative. Multiple programs spanning multiple sectors, with varied approaches and targets, were supported. This study found that much of the work relied on loose coalitions across City Government, with single agencies responsible for their own agendas, some with health co-benefits. Many policies were implemented through non-legislative mechanisms such as executive orders and the Health Code. Despite support from academic and some civil society groups, strong lobbying from industry and an unfavorable media led to some reforms being modified, legally challenged or blocked completely, particularly food environment modifiers. In contrast, reforms of the physical environment were described as highly consultative across and outside government and resulted in slower but more sustained reform.ConclusionThe Bloomberg administration was a "window of opportunity" with the imprimatur of the executive to progress a long-term, multi-faceted obesity prevention strategy, which has successfully reversed childhood trends. Through the involvement of external researchers and the extensive use of empirical data from a wide range of participants, this study offers a unique insight into the ways in which this was achieved. While some of the aspects of the reforms in New York City are unique to that setting at that time, there are important lessons that are transferable to other urban settings. These include: strong and consistent leadership; a commitment to innovative approaches and cross-sectoral collaboration; and a context to support and encourage this approach.

Dataset Information

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.

Publications

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets