Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
27,494
result(s) for
"Regeneration (Biology)"
Sort by:
It's still alive! : magical animals that regrow parts
\"Regenerative animals are survivors. Species with this ability can regrow limbs, skin, organs, and more! Find out how these animals use regeneration to evade predators and stay alive\"-- Provided by publisher.
Book
Cell fate specification and differentiation in the adult mammalian intestine
Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells — combined with redundant sources of niche signals — enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment. These new insights into stem cell regulation and fate specification could aid the development of therapies that exploit the regenerative capacity and functionality of the gut.The intestinal epithelium undergoes rapid turnover and is constantly exposed to hostile luminal contents. Recent insights from single-cell transcriptomics and organoid models have revealed that tissue repair is dependent on cell lineage plasticity and signals originating from different niche components.
Journal Article
Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis
Stem cells undergo dynamic changes in response to injury to regenerate lost cells. However, the identity of transitional states and the mechanisms that drive their trajectories remain understudied. Using lung organoids, multiple in vivo repair models, single-cell transcriptomics and lineage tracing, we find that alveolar type-2 epithelial cells undergoing differentiation into type-1 cells acquire pre-alveolar type-1 transitional cell state (PATS) en route to terminal maturation. Transitional cells undergo extensive stretching during differentiation, making them vulnerable to DNA damage. Cells in the PATS show an enrichment of TP53, TGFβ, DNA-damage-response signalling and cellular senescence. Gain and loss of function as well as genomic binding assays revealed a direct transcriptional control of PATS by TP53 signalling. Notably, accumulation of PATS-like cells in human fibrotic lungs was observed, suggesting persistence of the transitional state in fibrosis. Our study thus implicates a transient state associated with senescence in normal epithelial tissue repair and its abnormal persistence in disease conditions.After lung injury, Kobayashi, Tata et al. find an intermediate cell state during the transition of alveolar type-2 into type-1 cells that is associated with senescence, controlled by TP53 and persists in fibrosis.
Journal Article
The axolotl genome and the evolution of key tissue formation regulators
Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (
Ambystoma mexicanum
) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene
Pax3
. However, mutation of the axolotl
Pax3
paralogue
Pax7
resulted in an axolotl phenotype that was similar to those seen in
Pax3
−/−
and
Pax7
−/−
mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.
Sequencing and assembly of the 32-Gb genome of the Mexican axolotl reveals that it lacks the developmental gene
Pax3
, which is essential in other vertebrates; the genome sequence could improve our understanding of the evolution of the axolotl’s remarkable regenerative capabilities.
Axolotl genome sequence
Elly Tanaka, Eugene Myers and colleagues report the genome sequence of the axolotl, a model organism for developmental, regeneration and evolutionary studies. To sequence and assemble this large and complex genome, the authors used a combination of long- and short-read sequencing, optical mapping and a new genome assembly pipeline, MARVEL, optimized for long-read sequencing of complex genomes. The genome assembly shows an expansion of long terminal repeat retroelements and the presence of a large HoxA cluster, but also a reduction in the number of Pax-family genes in the genome of this popular salamander.
Journal Article
Articular cartilage regeneration by activated skeletal stem cells
Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage
1
. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation
2
–
4
. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis
5
–
7
. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.
Endogenous skeletal stem cells are recruited to form cartilage in mice when stimulated by microfracture surgery together with localized delivery of growth factors, pointing to a new approach for treating cartilage defects.
Journal Article
FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, committed to myogenic differentiation (primed state). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle.García-Prat, Perdiguero, Alonso-Martín et al. show that skeletal muscle contains a subpopulation of quiescent stem cells, maintained by FoxO signalling, that is preserved into late life but declines in advanced geriatric age.
Journal Article
T cell regeneration after immunological injury
Following periods of haematopoietic cell stress, such as after chemotherapy, radiotherapy, infection and transplantation, patient outcomes are linked to the degree of immune reconstitution, specifically of T cells. Delayed or defective recovery of the T cell pool has significant clinical consequences, including prolonged immunosuppression, poor vaccine responses and increased risks of infections and malignancies. Thus, strategies that restore thymic function and enhance T cell reconstitution can provide considerable benefit to individuals whose immune system has been decimated in various settings. In this Review, we focus on the causes and consequences of impaired adaptive immunity and discuss therapeutic strategies that can recover immune function, with a particular emphasis on approaches that can promote a diverse repertoire of T cells through de novo T cell formation.Reconstitution of the immune system after depletion by chemotherapy, radiotherapy, infection or transplantation is crucial to maintain protection from infection and to respond to immune-based therapy. Here the authors describe the ways in which a diverse T cell compartment can be restored, focusing on therapeutic strategies that drive the production of new T cells.
Journal Article
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration
Henry Sucov and colleagues demonstrate substantial natural variation in the capacity of the mouse heart to regenerate after injury and link this to the prevalence of mononuclear diploid cardiomyocytes. They identify
Tnni3k
as one gene that contributes to the observed variation and validate its role through mouse knockout and zebrafish overexpression studies.
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified
Tnni3k
as one gene that influences variation in this composition and demonstrated that
Tnni3k
knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of
Tnni3k
in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
Journal Article
Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor
An evolutionarily conserved alveolar epithelial progenitor lineage that derives from alveolar type 2 cells is responsive to Wnt signalling and acts as a major facultative progenitor in regenerating the distal lung.
A recipe for emergency alveoli
The lung, which relies on complex distal gas exchange units called alveoli for its function, is a highly quiescent organ, displaying a very low turnover of cells in its normal state. However, it is prone to environmental and infectious damaging agents. Elucidating how organs that are maintained in a mainly quiescent state regenerate after injury could help in the development of therapeutic strategies to promote organ repair. Edward Morrisey and colleagues have identified and characterized an alveolar epithelial progenitor that is responsive to Wnt and FGF7 signalling triggered by injury and that exists in mouse and human adult lungs. The human alveolar epithelial progenitors can be isolated and grown in three-dimensional organoids, highlighting their potential for future regeneration strategies.
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration
1
; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration
2
,
3
. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.
Journal Article