Biology subjects

Steiner, S. N.

Publications and source records attributed to Steiner, S. N..

3 recordsLinked to original sources

bioRxiv2025

Keratin 15 promotes a progenitor cell statein basal keratinocytes of skin epidermis

The type I intermediate filament proteins keratin 14 (K14) and keratin 15 (K15) are common to all complex epithelia. K14 is highly expressed by progenitor keratinocytes, in which it provides essential mechanical integrity and gates keratinocyte entry into differentiation by sequestering YAP1, a transcriptional effector of Hippo signaling, to the cytoplasm. K15 has long been used as a marker of hair bulge stem cells, though its specific role in skin epithelia is unknown. Here we show that the lack of two biochemical determinants, a cysteine residue within the stutter motif of the central rod domain and a 14-3-3 binding site in the N-terminal head domain, renders K15 unable to effectively sequester YAP1 in the cytoplasm like K14 does. We combine insight obtained from cell culture and transgenic mouse models with computational analyses of transcriptomics data and propose a model in which a higher K15:K14 ratio promotes a progenitor state and antagonizes differentiation in keratinocytes of the epidermis. SUMMARYThe type I intermediate filament keratin 15 (K15) exhibits preferential expression in a subset of skin keratinocytes with stem-like properties. We report that K15 promotes the progenitor state by counteracting the ability of the related K14 to negatively regulate YAP1, a terminal effector of Hippo signaling.

developmental biology↗

bioRxiv2024

MultiOmicsAgent: Guided extreme gradient-boosted decision trees-based approaches for biomarker-candidate discovery in multi-omics data

MultiOmicsAgent (MOAgent) is an innovative, Python based open-source tool for biomarker discovery, utilizing machine learning techniques specifically extreme gradient-boosted decision trees to process multi-omics data. With its cross-platform compatibility, user-oriented graphical interface and a well-documented API, MOAgent not only meets the needs of both coding professionals and those new to machine learning but also addresses common data analysis challenges like data incompleteness, class imbalances and data leakage between disjoint data splits. MOAgents guided data analysis strategy opens up data-driven insights from digitized clinical biospecimen cohorts and makes advanced data analysis accessible and reliable for a wide audience. Biographical NoteJens Settelmeier, Julia Boshart, Martin Gesell are Ph.D. candidates, Jianbo Fu, Sebastian N. Steiner are Post Doc candidates and Sandra Goetze, Patrick Pedrioli senior scientists at the Institute of Translational Medicine at Health Sciences and Technology department at ETH Zurich, Switzerland, within Professor Bernd Wollscheids research group who has been working in the fields of bioinformatics, clinical multi-omics with a focus on spatial cell surface proteomics. Peter J. Schuffler is professor at the institute of Pathology at the TU Munich, Germany and has been working in the field of digital pathology and clinical multi-modal studies. Diyora Salimova is junior professor at the department of Applied Mathematics at the Albert-Ludwigs-University of Freibug, Germany and has been working in the field of stochastic processes, approximation theory and machine learning related topics. Key PointsO_LIMOAgent enables a guided biomarker-candidate discovery in multi-omics studies, providing a graphical interface and well-documented API. C_LIO_LIA user can run MOAgent on a personal computer without the requirement of coding a single line. C_LIO_LIMOAgent is a Python-based solution for biomarker-candidate discovery, using machine learning to analyze multi-omics data. C_LIO_LIMOAgent can address challenges like data incompleteness and class imbalances, ensuring reliable analysis. C_LIO_LIMOAgent makes advanced data analysis accessible, enhancing insights from clinical data. C_LI

bioinformatics↗

bioRxiv2020

CD20 as a gatekeeper of the resting stage of human B cells

CD20 is a B cell specific membrane protein and a target of therapeutic antibodies such as rituximab (RTX)1. In spite of the prominent usage of anti-CD20 antibodies in the clinic little is known about the biological function of CD202. Here we show that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. A CRISPR/Cas-based ablation of CD20 in Ramos B cells results in a relocalisation of the IgM B cell antigen receptor (IgM-BCR) and the co-receptor CD19. The resulting IgM-BCR/CD19 signaling synapse leads to transient B cell activation followed by plasma cell differentiation. Similarly to CD20-deficient Ramos cells, naive human B cells treated with rituximab in vitro or isolated from patients during rituximab administration display hallmarks of transient activation characterized by the formation of the IgM-BCR/CD19 signaling synapse, followed by CD19 and IgM-BCR downregulation. Moreover, increased expression of specific plasma cell genes can be observed after rituximab treatment in relapsed CLL patients. In summary we identify CD20 as a gatekeeper of the resting state on human B cells and demonstrate that a disruption of the nanoscale organization of the B cell surface via CD20 deletion or anti-CD20 treatment profoundly alters B cell fate.

immunology↗