The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots to demonstrate that mouse haematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.
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http://dx.doi.org/10.1038/nature25741 | DOI Listing |
Sensors (Basel)
December 2024
2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
The widespread propagation of wireless communication devices, from smartphones and tablets to Internet of Things (IoT) systems, has become an integral part of modern life. However, the expansion of wireless technology has also raised public concern about the potential health risks associated with prolonged exposure to electromagnetic fields. Our objective is to determine the optimal machine learning model for constructing electric field strength maps across urban areas, enhancing the field of environmental monitoring with the aid of sensor-based data collection.
View Article and Find Full Text PDFBr J Anaesth
January 2025
Centre for Research and Improvement, Royal College of Anaesthetists, London, UK; Anaesthesia a Critical Care, Injury, Recovery and Inflammation Sciences, University of Nottingham, Nottingham, UK.
Background: Frailty and multimorbidity are common in older adults, but the prevalence and interaction of these conditions in surgical patients remain unclear. This study describes the clinical characteristics of a heterogeneous cohort of older UK surgical patients.
Methods: We conducted a prospective observational cohort study during 5 days in March 2022, aiming to recruit all UK patients aged 60 yr and older undergoing surgery, excluding minor procedures (e.
Clin Pharmacokinet
January 2025
Inria-Inserm COMPO Team, Centre Inria Sophia Antipolis-Méditerranée, CRCM, Inserm U1068-CNRS UMR7258-Aix-Marseille University UM105, Marseille, France.
Background: Cefotaxime is a widely prescribed cephalosporin antibiotic used to treat various infections. It is mainly eliminated unchanged by the kidney through tubular secretion and glomerular filtration. Therefore, a reduction of kidney function may increase exposure to the drug and induce toxic side effects.
View Article and Find Full Text PDFDevelopment
January 2025
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.
To maintain and regenerate adult tissues after injury, division and differentiation of tissue-resident stem cells must be precisely regulated. It remains elusive which regulatory strategies prevent exhaustion or overgrowth of the stem cell pool, whether there is coordination between multiple mechanisms, and how to detect them from snapshots. In Drosophila testes, somatic stem cells transition to a state that licenses them to differentiate, but remain capable of returning to the niche and resuming cell division.
View Article and Find Full Text PDFClin Colorectal Cancer
December 2024
Department of Surgery, HagaZiekenhuis, The Hague, The Netherlands.
Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.
Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers.
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