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Genetic programs operating in a history-dependent fashion are ubiquitous in nature and govern sophisticated processes such as development and differentiation. The ability to systematically and predictably encode such programs would advance the engineering of synthetic organisms and ecosystems with rich signal processing abilities. Here we implement robust, scalable history-dependent programs by distributing the computational labor across a cellular population. Our design is based on standardized recombinase-driven DNA scaffolds expressing different genes according to the order of occurrence of inputs. These multicellular computing systems are highly modular, do not require cell-cell communication channels, and any program can be built by differential composition of strains containing well-characterized logic scaffolds. We developed automated workflows that researchers can use to streamline program design and optimization. We anticipate that the history-dependent programs presented here will support many applications using cellular populations for material engineering, biomanufacturing and healthcare.
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http://dx.doi.org/10.1038/s41467-020-18455-z | DOI Listing |
Cell Mol Immunol
September 2025
Pediatric Intensive Care Unit, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences); Department of Immunology, School of Basic Medical Sciences; Department of Clinical Laboratory, the Third Affiliated Hospital of Southern Medical University, Southern Medical University, Gua
Communication between group 3 innate lymphoid cells (ILC3) and other immune cells, as well as intestinal epithelial cells, is pivotal in regulating intestinal inflammation. This study, for the first time, underscores the importance of crosstalk between intestinal endothelial cells (ECs) and ILC3. Our single-cell transcriptome analysis combined with protein expression detection revealed that ECs significantly increased the population of interleukin (IL)-22 ILC3 through interactions mediated by endothelin-1 (ET-1) and its receptor endothelin A receptor (EDNRA).
View Article and Find Full Text PDFNature
September 2025
Institute of Biomechanics and Medical Engineering, Applied Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing, China.
The human stomach features distinct, regionalized functionalities along the anterior-posterior axis. Historically, studies on stomach patterning have used animal models to identify the underlying principles. Recently, human pluripotent stem (hPS)-cell-based gastric organoids for modelling domain-specific development of the fundic and antral epithelium are emerging.
View Article and Find Full Text PDFNat Commun
September 2025
Department of Biochemistry, University of Illinois, Urbana-Champaign, IL, USA.
Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq.
View Article and Find Full Text PDFGenes Dev
September 2025
RU Adipocytes and Metabolism, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany;
Adipose tissue is rapidly expanding early in life. Elucidating the queues facilitating this process will advance our understanding of metabolically healthy obesity. Using single-cell RNA sequencing, we identified compositional differences of prewean and adult murine subcutaneous adipose tissue.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
August 2025
The Mikael Rayaan Foundation Global Transplantation and Cellular Therapy Consortium, Kansas City, KS; Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS; U.S Myeloma Innovations Research Collaborative, Kansas City, KS. Electronic addres
Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only curative option for myelofibrosis (MF) but is often underutilized in patients aged ≥ 65 due to concerns about treatment-related toxicity.
Methods: We conducted a retrospective analysis of chronic-phase MF allo-HCT recipients using the publicly available CIBMTR P-5640 dataset (2008-2019). Key endpoints included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), and graft-vs-host disease (GVHD)-related outcomes.