Transcriptional and Epigenetic Mechanisms Controlling Intestinal Cell Fate

2019 ◽  
pp. 259-286
Author(s):  
Fulvio Chiacchiera
Keyword(s):  
Cell Fate ◽  
Intestinal Cell ◽  
Epigenetic Mechanisms

scholarly journals Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity

2020 ◽  
Vol 16 (6) ◽  
pp. 1062-1080
Author(s):  
Jérémie Rispal ◽  
Fabrice Escaffit ◽  
Didier Trouche
Keyword(s):  
Signaling Pathways ◽  
Cell Fate ◽  
Chromatin Modification ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Cell Plasticity ◽  
Chromatin Dynamics ◽  
Irritable Bowel ◽  
The Many

AbstractThe rapid renewal of intestinal epithelium is mediated by a pool of stem cells, located at the bottom of crypts, giving rise to highly proliferative progenitor cells, which in turn differentiate during their migration along the villus. The equilibrium between renewal and differentiation is critical for establishment and maintenance of tissue homeostasis, and is regulated by signaling pathways (Wnt, Notch, Bmp…) and specific transcription factors (TCF4, CDX2…). Such regulation controls intestinal cell identities by modulating the cellular transcriptome. Recently, chromatin modification and dynamics have been identified as major actors linking signaling pathways and transcriptional regulation in the control of intestinal homeostasis. In this review, we synthesize the many facets of chromatin dynamics involved in controlling intestinal cell fate, such as stemness maintenance, progenitor identity, lineage choice and commitment, and terminal differentiation. In addition, we present recent data underlying the fundamental role of chromatin dynamics in intestinal cell plasticity. Indeed, this plasticity, which includes dedifferentiation processes or the response to environmental cues (like microbiota’s presence or food ingestion), is central for the organ’s physiology. Finally, we discuss the role of chromatin dynamics in the appearance and treatment of diseases caused by deficiencies in the aforementioned mechanisms, such as gastrointestinal cancer, inflammatory bowel disease or irritable bowel syndrome.

scholarly journals A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC)

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Imelda T Sandoval ◽  
Richard Glenn C Delacruz ◽  
Braden N Miller ◽  
Shauna Hill ◽  
Kristofor A Olson ◽  
...  
Keyword(s):  
Cell Fate ◽  
Adenomatous Polyposis Coli ◽  
Normal Development ◽  
Intestinal Cell ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Pyruvate Metabolism ◽  
Metabolic Switch ◽  
Intestinal Differentiation ◽  
Mitochondrial Pyruvate Carrier

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc.

scholarly journals Epigenetic Regulation of Cell-Fate Changes That Determine Adult Liver Regeneration After Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Luigi Aloia
Keyword(s):  
Liver Disease ◽  
Cell Fate ◽  
Tissue Injury ◽  
The Body ◽  
Epigenetic Mechanisms ◽  
Adult Liver ◽  
Cell Fate Decisions ◽  
Epithelial Regeneration ◽  
Cellular Turnover ◽  
Chromatin Modifiers

The adult liver has excellent regenerative potential following injury. In contrast to other organs of the body that have high cellular turnover during homeostasis (e.g., intestine, stomach, and skin), the adult liver is a slowly self-renewing organ and does not contain a defined stem-cell compartment that maintains homeostasis. However, tissue damage induces significant proliferation across the liver and can trigger cell-fate changes, such as trans-differentiation and de-differentiation into liver progenitors, which contribute to efficient tissue regeneration and restoration of liver functions. Epigenetic mechanisms have been shown to regulate cell-fate decisions in both embryonic and adult tissues in response to environmental cues. Underlying their relevance in liver biology, expression levels and epigenetic activity of chromatin modifiers are often altered in chronic liver disease and liver cancer. In this review, I examine the role of several chromatin modifiers in the regulation of cell-fate changes that determine efficient adult liver epithelial regeneration in response to tissue injury in mouse models. Specifically, I focus on epigenetic mechanisms such as chromatin remodelling, DNA methylation and hydroxymethylation, and histone methylation and deacetylation. Finally, I address how altered epigenetic mechanisms and the interplay between epigenetics and metabolism may contribute to the initiation and progression of liver disease and cancer.

Notch Pathway Regulation of Intestinal Cell Fate

2012 ◽  
pp. 329-357 ◽  
Author(s):  
Kelli L. Van Dussen ◽  
Peter J. Dempsey ◽  
Linda C. Samuelson
Keyword(s):  
Cell Fate ◽  
Notch Pathway ◽  
Intestinal Cell ◽  
Pathway Regulation

‘Enhancing’ red cell fate through epigenetic mechanisms

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Marlies P. Rossmann ◽  
Leonard I. Zon
Keyword(s):  
Cell Fate ◽  
Epigenetic Mechanisms ◽  
Red Cell

scholarly journals Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Ruoxi Wang ◽  
Yu Wang ◽  
Lisha Zhu ◽  
Yan Liu ◽  
Weiran Li
Keyword(s):  
Regenerative Medicine ◽  
Cell Fate ◽  
Large Scale ◽  
Functional Decline ◽  
Cell Aging ◽  
Epigenetic Mechanisms ◽  
Reliable Source ◽  
Regenerative Therapies

Mesenchymal stem cells (MSCs) are a reliable source for cell-based regenerative medicine owing to their multipotency and biological functions. However, aging-induced systemic homeostasis disorders in vivo and cell culture passaging in vitro induce a functional decline of MSCs, switching MSCs to a senescent status with impaired self-renewal capacity and biased differentiation tendency. MSC functional decline accounts for the pathogenesis of many diseases and, more importantly, limits the large-scale applications of MSCs in regenerative medicine. Growing evidence implies that epigenetic mechanisms are a critical regulator of the differentiation programs for cell fate and are subject to changes during aging. Thus, we here review epigenetic dysregulations that contribute to MSC aging and osteoporosis. Comprehending detailed epigenetic mechanisms could provide us with a novel horizon for dissecting MSC-related pathogenesis and further optimizing MSC-mediated regenerative therapies.

Sign in / Sign up

Export Citation Format

Share Document