Reprogramming cellular identity during intestinal regeneration

DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains.

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Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila

Nature Cell Biology ◽

10.1038/s41556-021-00674-1 ◽

2021 ◽

Author(s):

Vasilia Tamamouna ◽

M. Mahidur Rahman ◽

Monika Petersson ◽

Irini Charalambous ◽

Kristina Kux ◽

...

Keyword(s):

Intestinal Regeneration

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Antibiotics Modulate Intestinal Regeneration

Biology ◽

10.3390/biology10030236 ◽

2021 ◽

Vol 10 (3) ◽

pp. 236

Author(s):

Lymarie M. Díaz-Díaz ◽

Natalia Rosario-Meléndez ◽

Andrea Rodríguez-Villafañe ◽

Yariel Y. Figueroa-Vega ◽

Omar A. Pérez-Villafañe ◽

...

Keyword(s):

Cell Proliferation ◽

Sea Cucumber ◽

Regenerative Processes ◽

Ecm Remodeling ◽

Bacterial Cultures ◽

Intestinal Regeneration ◽

Negative Effect ◽

Altered Cell ◽

Holothuria Glaberrima ◽

Mtt Assays

The increased antibiotics usage in biomedical and agricultural settings has been well documented. Antibiotics have now been shown to exert effects outside their purposive use, including effects on physiological and developmental processes. We explored the effect of various antibiotics on intestinal regeneration in the sea cucumber Holothuria glaberrima. For this, holothurians were eviscerated and left to regenerate for 10 days in seawater with different penicillin/streptomycin-based cocktails (100 µg/mL PS) including: 100 µg/mL kanamycin (KPS), 5 µg/mL vancomycin (VPS), and 4 µg/mL (E4PS) or 20 µg/mL (E20PS) erythromycin. Immunohistological and histochemical analyses were performed to analyze regenerative processes, including rudiment size, extracellular matrix (ECM) remodeling, cell proliferation, and muscle dedifferentiation. A reduction in muscle dedifferentiation was observed in all antibiotic-treated animals. ECM remodeling was decreased by VPS, E4PS, and E20PS treatments. In addition, organisms subjected to E20PS displayed a significant reduction in the size of their regenerating rudiments while VPS exposure altered cell proliferation. MTT assays were used to discard the possibility that the antibiotics directly affect holothurian metabolic activity while bacterial cultures were used to test antibiotic effects on holothurian enteric microbiota. Our results demonstrate a negative effect on intestinal regeneration and strongly suggest that these effects are due to alterations in the microbial community.

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Sestrin protects Drosophila midgut from mercury chloride-induced damage by inhibiting oxidative stress and stimulating intestinal regeneration

Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology ◽

10.1016/j.cbpc.2021.109083 ◽

2021 ◽

pp. 109083

Author(s):

Zhi Chen ◽

Wen Zhang ◽

Fen Wang ◽

Ren Mu ◽

Di Wen

Keyword(s):

Oxidative Stress ◽

Mercury Chloride ◽

Intestinal Regeneration

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A generalization of t-SNE and UMAP to single-cell multimodal omics

Genome Biology ◽

10.1186/s13059-021-02356-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Van Hoan Do ◽

Stefan Canzar

Keyword(s):

Dimensionality Reduction ◽

Single Cell ◽

Cell Types ◽

High Dimensional ◽

Omics Data ◽

Relative Contribution ◽

Reduction Techniques ◽

Dimensionality Reduction Techniques ◽

Concise Representation ◽

Cellular Identity

AbstractEmerging single-cell technologies profile multiple types of molecules within individual cells. A fundamental step in the analysis of the produced high-dimensional data is their visualization using dimensionality reduction techniques such as t-SNE and UMAP. We introduce j-SNE and j-UMAP as their natural generalizations to the joint visualization of multimodal omics data. Our approach automatically learns the relative contribution of each modality to a concise representation of cellular identity that promotes discriminative features but suppresses noise. On eight datasets, j-SNE and j-UMAP produce unified embeddings that better agree with known cell types and that harmonize RNA and protein velocity landscapes.

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