Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration

Srinivas Allanki; Boris Strilic; Lilly Scheinberger; Yeszamin L. Onderwater; Alora Marks; Stefan Günther; Jens Preussner; Khrievono Kikhi; Mario Looso; Didier Y. R. Stainier; Sven Reischauer

doi:10.1126/sciadv.abg6497

Hypoxia in Cell Reprogramming and the Epigenetic Regulations

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.609984 ◽

2021 ◽

Vol 9 ◽

Author(s):

Nariaki Nakamura ◽

Xiaobing Shi ◽

Radbod Darabi ◽

Yong Li

Keyword(s):

Cell Proliferation ◽

Cell Fate ◽

Tissue Regeneration ◽

Cellular Reprogramming ◽

Cell Reprogramming ◽

Cell Renewal ◽

Cellular Functions ◽

Stem Cell Renewal ◽

Epigenetic Regulations

Cellular reprogramming is a fundamental topic in the research of stem cells and molecular biology. It is widely investigated and its understanding is crucial for learning about different aspects of development such as cell proliferation, determination of cell fate and stem cell renewal. Other factors involved during development include hypoxia and epigenetics, which play major roles in the development of tissues and organs. This review will discuss the involvement of hypoxia and epigenetics in the regulation of cellular reprogramming and how interplay between each factor can contribute to different cellular functions as well as tissue regeneration.

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Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation

Annual Review of Medicine ◽

10.1146/annurev-med-041818-011649 ◽

2020 ◽

Vol 71 (1) ◽

pp. 263-276 ◽

Cited By ~ 11

Author(s):

Stuart A. Cook ◽

Sebastian Schafer

Keyword(s):

Tissue Regeneration ◽

Inflammatory Diseases ◽

Parenchymal Cell ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Cell Dysfunction ◽

Tissue Integrity ◽

Polarized Cells ◽

Inflammatory Bowel ◽

Interleukin 11

Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases—myofibroblast activation, parenchymal cell dysfunction, and inflammation—while also inhibiting tissue regeneration. This cytokine has been little studied, and publications on IL-11 peaked in the early 1990s, when it was largely misunderstood. Here we describe recent advances in our understanding of IL-11 biology, outline how misconceptions as to its function came about, and highlight the large potential of therapies targeting IL-11 signaling for treating human disease.

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Editorial: Regulation of Cellular Reprogramming for Post-stroke Tissue Regeneration: Bridging a Gap Between Basic Research and Clinical Application

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.793900 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jing Wang ◽

Cindi M. Morshead ◽

Gong Chen ◽

Wen Li

Keyword(s):

Clinical Application ◽

Tissue Regeneration ◽

Basic Research ◽

Cellular Reprogramming ◽

Post Stroke

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Hepatocyte generation in liver homeostasis, repair, and regeneration

Cell Regeneration ◽

10.1186/s13619-021-00101-8 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Wenjuan Pu ◽

Bin Zhou

Keyword(s):

Cell Fate ◽

Tissue Regeneration ◽

Cell Lineage ◽

Lineage Tracing ◽

Cellular Reprogramming ◽

Hepatocyte Proliferation ◽

Genetic Lineage ◽

Regenerative Capacity ◽

The Past ◽

Genetic Lineage Tracing

AbstractThe liver has remarkable capability to regenerate, employing mechanism to ensure the stable liver-to-bodyweight ratio for body homeostasis. The source of this regenerative capacity has received great attention over the past decade yet still remained controversial currently. Deciphering the sources for hepatocytes provides the basis for understanding tissue regeneration and repair, and also illustrates new potential therapeutic targets for treating liver diseases. In this review, we describe recent advances in genetic lineage tracing studies over liver stem cells, hepatocyte proliferation, and cell lineage conversions or cellular reprogramming. This review will also evaluate the technical strengths and limitations of methods used for studies on hepatocyte generation and cell fate plasticity in liver homeostasis, repair and regeneration.

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Fetal-like reversion in the regenerating intestine is regulated by mesenchymal Asporin

10.1101/2021.06.24.449590 ◽

2021 ◽

Author(s):

Sharif Iqbal ◽

Simon Andersson ◽

Ernesta Nestaite ◽

Nalle Pentinmikko ◽

Ashish Kumar ◽

...

Keyword(s):

Extracellular Matrix ◽

Tissue Regeneration ◽

Tissue Repair ◽

Ex Vivo ◽

Cellular Reprogramming ◽

Tissue Homeostasis ◽

Epithelial Injury ◽

Epithelial Regeneration ◽

Tgfβ Signalling ◽

Small Intestinal

Epithelial tissues undergo fetal-like cellular reprogramming to regenerate after damage1,2. Although the mesenchyme and the extracellular matrix (ECM) play critical roles in tissue homeostasis and regeneration2-5, their role in repurposing developmental programs in epithelium is unknown. To model epithelial regeneration, we culture intestinal epithelium on decellularized small intestinal scaffold (iECM), and identify Asporin (Aspn), an ECM bound proteoglycan, as a critical mediator of cellular reprogramming. Aspn is produced by the mesenchyme, and we show that its effect on epithelial Tgfβ-signalling via CD44 is critical for fetal-like conversion. Furthermore, we demonstrate that Aspn is transiently increased upon chemotherapy-induced damage and pivotal for a timely induction of the fetal-like state and tissue regeneration. In summary, we establish a platform for modelling epithelial injury responses ex vivo, and show that the mesenchymal Aspn-producing niche controls tissue repair by regulating epithelial fetal-like reprogramming.

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Decellularized bone extracellular matrix in skeletal tissue engineering

Biochemical Society Transactions ◽

10.1042/bst20190079 ◽

2020 ◽

Vol 48 (3) ◽

pp. 755-764

Author(s):

Benjamin B. Rothrauff ◽

Rocky S. Tuan

Keyword(s):

Tissue Engineering ◽

Bone Regeneration ◽

Tissue Regeneration ◽

Animal Studies ◽

Tumor Resection ◽

Regenerative Capacity ◽

Skeletal Tissue ◽

Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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