bims-gerecp 2024-03-31 papers

Issue of 2024–03–31
five papers selected by
Xiao Qin, University of Oxford

Nat Commun. 2024 Mar 29. 15(1): 2744

Gene-expression memory-based prediction of cell lineages from scRNA-seq datasets.

A S Eisele, M Tarbier, A A Dormann, V Pelechano, D M Suter.

Assigning single cell transcriptomes to cellular lineage trees by lineage tracing has transformed our understanding of differentiation during development, regeneration, and disease. However, lineage tracing is technically demanding, often restricted in time-resolution, and most scRNA-seq datasets are devoid of lineage information. Here we introduce Gene Expression Memory-based Lineage Inference (GEMLI), a computational tool allowing to robustly identify small to medium-sized cell lineages solely from scRNA-seq datasets. GEMLI allows to study heritable gene expression, to discriminate symmetric and asymmetric cell fate decisions and to reconstruct individual multicellular structures from pooled scRNA-seq datasets. In human breast cancer biopsies, GEMLI reveals previously unknown gene expression changes at the onset of cancer invasiveness. The universal applicability of GEMLI allows studying the role of small cell lineages in a wide range of physiological and pathological contexts, notably in vivo. GEMLI is available as an R package on GitHub ( https://github.com/UPSUTER/GEMLI ).

DOI: https://doi.org/10.1038/s41467-024-47158-y

Nat Methods. 2024 Mar 25.

Assessing GPT-4 for cell type annotation in single-cell RNA-seq analysis.

Wenpin Hou, Zhicheng Ji.

Here we demonstrate that the large language model GPT-4 can accurately annotate cell types using marker gene information in single-cell RNA sequencing analysis. When evaluated across hundreds of tissue and cell types, GPT-4 generates cell type annotations exhibiting strong concordance with manual annotations. This capability can considerably reduce the effort and expertise required for cell type annotation. Additionally, we have developed an R software package GPTCelltype for GPT-4's automated cell type annotation.

DOI: https://doi.org/10.1038/s41592-024-02235-4

Nat Commun. 2024 Mar 29. 15(1): 2765

DELVE: feature selection for preserving biological trajectories in single-cell data.

Jolene S Ranek, Wayne Stallaert, J Justin Milner, Margaret Redick, Samuel C Wolff, Adriana S Beltran, Natalie Stanley, Jeremy E Purvis.

Single-cell technologies can measure the expression of thousands of molecular features in individual cells undergoing dynamic biological processes. While examining cells along a computationally-ordered pseudotime trajectory can reveal how changes in gene or protein expression impact cell fate, identifying such dynamic features is challenging due to the inherent noise in single-cell data. Here, we present DELVE, an unsupervised feature selection method for identifying a representative subset of molecular features which robustly recapitulate cellular trajectories. In contrast to previous work, DELVE uses a bottom-up approach to mitigate the effects of confounding sources of variation, and instead models cell states from dynamic gene or protein modules based on core regulatory complexes. Using simulations, single-cell RNA sequencing, and iterative immunofluorescence imaging data in the context of cell cycle and cellular differentiation, we demonstrate how DELVE selects features that better define cell-types and cell-type transitions. DELVE is available as an open-source python package: https://github.com/jranek/delve .

DOI: https://doi.org/10.1038/s41467-024-46773-z

Nat Commun. 2024 Mar 26. 15(1): 2656

Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor.

Xingting Guo, Chenhui Wang, Yongchao Zhang, Ruxue Wei, Rongwen Xi.

The manipulation of cell identity by reprograming holds immense potential in regenerative medicine, but is often limited by the inefficient acquisition of fully functional cells. This problem can potentially be resolved by better understanding the reprogramming process using in vivo genetic models, which are currently scarce. Here we report that both enterocytes (ECs) and enteroendocrine cells (EEs) in adult Drosophila midgut show a surprising degree of cell plasticity. Depleting the transcription factor Tramtrack in the differentiated ECs can initiate Prospero-mediated cell transdifferentiation, leading to EE-like cells. On the other hand, depletion of Prospero in the differentiated EEs can lead to the loss of EE-specific transcription programs and the gain of intestinal progenitor cell identity, allowing cell cycle re-entry or differentiation into ECs. We find that intestinal progenitor cells, ECs, and EEs have a similar chromatin accessibility profile, supporting the concept that cell plasticity is enabled by pre-existing chromatin accessibility with switchable transcription programs. Further genetic analysis with this system reveals that the NuRD chromatin remodeling complex, cell lineage confliction, and age act as barriers to EC-to-EE transdifferentiation. The establishment of this genetically tractable in vivo model should facilitate mechanistic investigation of cell plasticity at the molecular and genetic level.

DOI: https://doi.org/10.1038/s41467-024-46956-8

Cells. 2024 Mar 12. pii: 495. [Epub ahead of print]13(6):

Diversity of Intercellular Communication Modes: A Cancer Biology Perspective.

Thanzeela Ebrahim, Abdul Shukkur Ebrahim, Mustapha Kandouz.

From the moment a cell is on the path to malignant transformation, its interaction with other cells from the microenvironment becomes altered. The flow of molecular information is at the heart of the cellular and systemic fate in tumors, and various processes participate in conveying key molecular information from or to certain cancer cells. For instance, the loss of tight junction molecules is part of the signal sent to cancer cells so that they are no longer bound to the primary tumors and are thus free to travel and metastasize. Upon the targeting of a single cell by a therapeutic drug, gap junctions are able to communicate death information to by-standing cells. The discovery of the importance of novel modes of cell-cell communication such as different types of extracellular vesicles or tunneling nanotubes is changing the way scientists look at these processes. However, are they all actively involved in different contexts at the same time or are they recruited to fulfill specific tasks? What does the multiplicity of modes mean for the overall progression of the disease? Here, we extend an open invitation to think about the overall significance of these questions, rather than engage in an elusive attempt at a systematic repertory of the mechanisms at play.

Keywords: adherens junction; apoptotic bodies; bystander effect; cancer; desmosome; eph; ephrin; exosome; extracellular vesicle; gap junction; intercellular communication; tight junction; tunelling nanotube

DOI: https://doi.org/10.3390/cells13060495