Cold Spring Harbor Perspectives in Biology

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EISSN : 1943-0264
Published by: Cold Spring Harbor Laboratory (10.1101)
Total articles ≅ 1,510
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Yingchao Xue, Sashank K. Reddy,
Cold Spring Harbor Perspectives in Biology;

Effective tissue repair is vital for the survival of organisms. Yet, how the immune system coordinates with tissue stem cells (SCs) to effect postnatal tissue restoration remains elusive. This review presents current knowledge surrounding wound-induced SC and immune signaling that favors tissue repair, including wound healing and regeneration. We discuss factors that affect regenerative capacities among organisms and the dynamics of local immune cells and SCs during reepithelialization. We also present recent insights into how immune niches communicate with SCs or other body systems to restore the epithelial architecture. Additionally, we summarize our findings on functional wound regeneration, specifically how alarmin (double-stranded RNA [dsRNA])-activated Toll-like receptor signaling and host–microbe interaction-related immune pathways alter the regenerative property of skin SCs. Last, we touch on mechanisms by which known immunologic cellular and molecular signaling might boost the skin's regenerative property. Overall, this review will provide insights into how therapeutically modulating immune signaling could enhance postnatal tissue regeneration.
Adam P.W. Johnston, Freda D. Miller
Cold Spring Harbor Perspectives in Biology;

Animals such as amphibians have an incredible capacity for regeneration with some being able to regrow their tail or appendages. Although some mammalian tissues like the skin and bones can repair following injury, there are only a few examples of true multilineage regeneration, including the distal portion of the digit tip. In both amphibians and mammals, however, to achieve successful repair or regeneration, it is now appreciated that intact nerve innervation is a necessity. Here, we review the current state of literature and discuss recent advances that identify axon-derived signals, Schwann cells, and nerve-derived mesenchymal cells as direct and indirect supporters of adult tissue homeostasis and repair. We posit that understanding how nerves positively influence repair and regeneration could lead to targeted regenerative medicine strategies to enhance tissue repair in humans.
Robert J. Handa, Julietta A. Sheng, Emily A. Castellanos, Hayley N. Templeton, Robert F. McGivern
Cold Spring Harbor Perspectives in Biology;

Sex differences in the neuroendocrine response to acute stress occur in both animals and humans. In rodents, stressors such as restraint and novelty induce a greater activation of the hypothalamic-pituitary-adrenal axis (HPA) in females compared to males. The nature of this difference arises from steroid actions during development (organizational effects) and adulthood (activational effects). Androgens decrease HPA stress responsivity to acute stress, while estradiol increases it. Androgenic down-regulation of HPA responsiveness is mediated by the binding of testosterone (T) and dihydrotestosterone (DHT) to the androgen receptor, as well as the binding of the DHT metabolite, 3β-diol, to the β form of the estrogen receptor (ERβ). Estradiol binding to the α form of the estrogen receptor (ERα) increases HPA responsivity. Studies of human sex differences are relatively few and generally employ a psychosocial paradigm to measure stress-related HPA activation. Men consistently show greater HPA reactivity than women when being evaluated for achievement. Some studies have found greater reactivity in women when being evaluated for social performance. The pattern is inconsistent with rodent studies but may involve the differential nature of the stressors employed. Psychosocial stress is nonphysical and invokes a significant degree of top-down processing that is not easily comparable to the types of stressors employed in rodents. Gender identity may also be a factor based on recent work showing that it influences the neural processing of positive and negative emotional stimuli independent of genetic sex. Comparing different types of stressors and how they interact with gender identity and genetic sex will provide a better understanding of sex steroid influences on stress-related HPA reactivity.
Clarisse Ganier, Emanuel Rognoni, Georgina Goss, Magnus Lynch, Fiona M. Watt
Cold Spring Harbor Perspectives in Biology, Volume 14;

Fibroblasts are the main cell type in the dermis. They are responsible for the synthesis and deposition of structural proteins such as collagen and elastin, which are integrated into the extracellular matrix (ECM). Mouse and human studies using flow cytometry, cell culture, skin reconstitution, and lineage tracing experiments have shown the existence of different subpopulations of fibroblasts, including papillary fibroblasts, reticular fibroblasts, and fibroblasts comprising the dermal papilla at the base of the hair follicle. In recent years, the technological advances in single-cell sequencing have allowed researchers to study the repertoire of cells present in full-thickness skin including the dermis. Multiple groups have confirmed that distinct fibroblast populations can be identified in mouse and human dermis on the basis of differences in the transcriptional profile. Here, we discuss the current state of knowledge regarding dermal fibroblast heterogeneity in healthy mouse and human skin, highlighting the similarities and differences between mouse and human fibroblast subpopulations. We also discuss how fibroblast heterogeneity may provide insights into physiological wound healing and its dysfunction in pathological states such as hypertrophic and keloid scars.
Dongqing Li, Guanglin Niu,
Cold Spring Harbor Perspectives in Biology;

An increasing number of noncoding RNAs (ncRNAs) have been found to regulate gene expression and protein functions, playing important roles in diverse biological processes and diseases. Their crucial functions have been reported in almost every cell type and all stages of skin wound healing. Evidence of their pathogenetic roles in common wound complications, such as chronic nonhealing wounds and excessive scarring, is also accumulating. Given their unique expression and functional properties, ncRNAs are promising therapeutic and diagnostic entities. In this review, we discuss current knowledge about the functional roles of noncoding elements, such as microRNAs, long ncRNAs, and circular RNAs, in skin wound healing, focusing on in vivo evidence from studies of human wound samples and animal wound models. Finally, we provide a perspective on the outlook of ncRNA-based therapeutics in wound care.
James C. Walton, Jacob R. Bumgarner, Randy J. Nelson
Cold Spring Harbor Perspectives in Biology;

Sex as a biological variable is the focus of much literature and has been emphasized by the National Institutes of Health, in part, to remedy a long history of male-dominated studies in preclinical and clinical research. We propose that time-of-day is also a crucial biological variable in biomedical research. In common with sex differences, time-of-day should be considered in analyses and reported to improve reproducibility of studies and to provide the appropriate context to the conclusions. Endogenous circadian rhythms are present in virtually all living organisms, including bacteria, plants, invertebrates, and vertebrates. Virtually all physiological and behavioral processes display daily fluctuations in optimal performance that are driven by these endogenous circadian clocks; importantly, many of those circadian rhythms also show sex differences. In this review, we describe some of the documented sex differences in circadian rhythms.
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