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Articles by Benjamin D. Simons
Sexual dimorphism in epidermal stem cell dynamics
Abstract The epidermis is a stratified epithelium comprising proliferative basal cells and differentiated suprabasal cells that are continuously renewed throughout life. Conflicting theories have been proposed regarding the heterogeneity of the basal cell layer, with some studies proposing that all proliferative cells have self-renewal potential during homeostasis1,2,3,4,5.
The temporal architecture of the seminiferous epithelial cycle revealed by spatial transcriptomics
Keywords spatial transcriptomics seqFISH+ seminiferous epithelial cycle spermatogenesis Sertoli cells biological oscillator retinoic acid temporal dynamics mouse testis cell-cell signaling cell synchronization spatial biology Wnt signaling permissive signal blood-testis barrier Get full text access Log in, subscribe or purchase for full access. References 1. Green, C.D. ∙ Ma, Q. ∙ Manske, G.L. ... A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq Dev. Cell.
Early fibrotic niches establish tumour-permissive microenvironments
Abstract Pathologic transformation represents a critical yet poorly defined window during which mutant epithelial stem cells actively construct the microenvironment that enables tumour initiation1,2. Here using integrated single-cell, spatial and functional analyses, we define the earliest multicellular events that licence this transition following oncogenic activation in the lung.
Lifting regenerative barriers promotes epithelial cell fate plasticity supporting lineage conversion - Nature Communications
Abstract The ability of adult epithelial cells to rewire their cell fate programme in response to injury has emerged as a new paradigm in stem cell biology. This plasticity supersedes the concept of strict stem cell hierarchies, granting cells access to a wider repertoire of fate choices. Yet, in order to prevent a disordered cellular response, this process must be finely regulated.
Author Correction: Mechanisms of stretch-mediated skin expansion at single-cell resolution - Nature
Correction to: Nature https://doi.org/10.1038/s41586-020-2555-7 Published online 29 July 2020 In the version of the article initially published, in Extended Data Fig. 10e, the immunohistochemistry staining for FOSL1 on the treated sample (Trametinib) contained incorrect data that were identical to those shown in Fig. 3d but acquired at different magnification. This mistake was due to an error in saving the image under the wrong name following its microscopic acquisition.
A computational pipeline for spatial mechano-transcriptomics - Nature Methods
Abstract Advances in spatial profiling technologies are providing insights into how molecular programs are influenced by local signaling and environmental cues. However, cell fate specification and tissue patterning involve the interplay of biochemical and mechanical feedback. Here we develop a computational framework that enables the joint statistical analysis of transcriptional and mechanical signals in the context of spatial transcriptomics.
Sustained NF-κB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation
Keywords clonal modeling lung stem cells regeneration program NF-κB activation tumor ecosystem dynamics cell plasticity stem cell competition lung cancer tumor evolution lineage tracing AT2 clone dynamics cell fate plasticity Introduction Tissues deploy intricate reparative programs to restore homeostasis after injury.
OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma - Nature Communications
Abstract Functional cellular heterogeneity in tumours often underlies incomplete response to therapy and relapse. Previously, we demonstrated that the growth of the paediatric brain malignancy, sonic hedgehog subgroup medulloblastoma, is rooted in a dysregulated developmental hierarchy, the apex of which is defined by characteristically quiescent SOX2+ stem-like cells.
Spatial Transcriptomics Reveals the Temporal Architecture of the Seminiferous Epithelial Cycle and Precise Sertoli-Germ Synchronization
Abstract Spermatogenesis is characterized by the seminiferous epithelial cycle, a periodic pattern of germ cell differentiation with a wave-like progression along the length of seminiferous tubules. While key signaling and metabolic components of the cycle are known, the transcriptional changes across the cycle and the correlations between germ cell and somatic lineages remain undefined.
Mechanisms that clear mutations drive field cancerization in mammary tissue - Nature
Abstract Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1,2,3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1−/−;Trp53−/− cells, and find that both follow a similar pattern of loss and spread within ducts.
Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice - Nature Communications
Abstract Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected.
Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence
Highlights • Plasma cells show extended lifespan in vivo with broad heterogeneity • Lifespan distribution and variation between antigens imply critical dynamics • Competition over survival factors self-tunes gene network to critical regime • Self-tuning by competition is beneficial for the long-term regulation of immune memory Summary Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist for decades,...
Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal
Highlights • Pits of extramural peribiliary glands homeostatically renew the surface epithelium • Bases of mural peribiliary glands homeostatically renew the surface epithelium • Graded gene expression defines compartments, which could be modulated diurnally • Canonical Wnt signaling controls biliary epithelial identity Summary The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits.
Central NY ag community suffers a great loss but leaves a great legacy
I am writing this article with a heavy heart. We in the agricultural community have lost three very influential people here in Central New York. I was so honored and blessed to have worked with these people in my many capacities with Farm Bureau, Fair Association, the Oneida Co. Association of Towns and the Boonville Milk Co-op. Hubert Pritchard Hubert Andrew Pritchard, 81, of Westmoreland, passed away on July 6. He was active in the FFA at the school and state levels.
Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms - Nature Cancer
Abstract Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes.
Inflationary theory of branching morphogenesis in the mouse salivary gland - Nature Communications
Abstract The mechanisms that regulate the patterning of branched epithelia remain a subject of long-standing debate. Recently, it has been proposed that the statistical organization of multiple ductal tissues can be explained through a local self-organizing principle based on the branching-annihilating random walk (BARW) in which proliferating tips drive a process of ductal elongation and stochastic bifurcation that terminates when tips encounter maturing ducts.
Author Correction: A cellular hierarchy in melanoma uncouples growth and metastasis - Nature
Author notes Ignacio Bordeu Present address: Departamento de Física, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile Florian Rambow Present address: Department of Applied Computational Cancer Research, Institute for AI in Medicine (IKIM), University Hospital Essen, Essen, Germany Florian Rambow Present address: University Duisburg-Essen, Essen, Germany Florian Rambow Present address: German Cancer Consortium (DKTK), partner site Essen, Essen, Germany These...
A cellular hierarchy in melanoma uncouples growth and metastasis - Nature
Abstract Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations.
Retrograde movements determine effective stem cell numbers in the intestine - Nature
Abstract The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different sites is unknown.
Transient suppression of transplanted spermatogonial stem cell differentiation restores fertility in mice
Highlights • Following transplantation, spermatogonial stem cells follow stochastic clone dynamics • Most initially settled stem cells are lost through chance differentiation and death • Donor cell differentiation can be suppressed using a retinoic acid synthesis inhibitor • Transient differentiation block boosts repopulation and restores fertility of the host Summary A remarkable feature of tissue stem cells is their ability to regenerate the structure and function of host tissue following...
Stem cell lineage survival as a noisy competition for niche access
Stem cell lineage survival as a noisy competition for niche access Bernat Corominas-Murtra, Colinda L. G. J. Scheele, Kasumi Kishi, Saskia I. J. Ellenbroek, Benjamin D. Simons, Jacco van Rheenen, Edouard Hannezo Proceedings of the National Academy of Sciences Jul 2020, 201921205; DOI: 10.1073/pnas.1921205117
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