Advances in Anatomy Embryology and Cell Biology最新文献

The regulation of mRNA transcription and translation is uncoupled during oogenesis. The reason for this uncoupling is two-fold. Chromatin is only accessible to the transcriptional machinery during the growth phase as it condenses prior to resumption of meiosis to ensure faithful segregation of chromosomes during meiotic maturation. Thus, transcription rates are high during this time period in order to produce all of the transcripts needed for meiosis, fertilization, and embryo cleavage until the newly formed embryonic genome becomes transcriptionally active. To ensure appropriate timing of key developmental milestones including chromatin condensation, resumption of meiosis, segregation of chromosomes, and polar body extrusion, the translation of protein from transcripts synthesized during oocyte growth must be temporally regulated. This is achieved by the regulation of mRNA interaction with RNA binding proteins and shortening and lengthening of the poly(A) tail. This chapter details the essential factors that regulate the dynamic changes in mRNA synthesis, storage, translation, and degradation during oocyte growth and maturation.

The existence of functionally diverse and plastic β cells in islets of Langerhans has been reported since the 1980s. Recently, high-resolution technologies have advanced our understanding of β-cell heterogeneity and plasticity. Here, we define plasticity broadly as dynamic changes in cellular phenotypes and heterogeneity as differences in cellular behaviors. Individual β cells react differently to environmental challenges and act together to maintain β-cell mass and glucose homeostasis within a narrow range of 70-140 mg/dL. During the progress of diabetes, this elaborate balance is disrupted, and a lack of β-cell compensation leads to dysregulated blood glucose. In this chapter, we assess β-cell stress that instigates increased β-cell heterogeneity and adaptive β-cell responses such as proliferation, dedifferentiation, maturity, and insulin secretion. We also discuss the maturity, electrical activity, and insulin secretion of well-characterized β-cell subgroups. Finally, we touch upon the plasticity of other non-β pancreatic cells and their cooperation with β cells to maintain homeostasis.

Pancreatic δ cells act locally to repress both insulin and glucagon secretion. Because they are a rare cell type, experimentation examining δ-cell function and control has lagged that of the more abundant α and β cells. Emerging evidence, enabled partly by developing single-cell technology, demonstrates that δ-cell function is, in part, directed by δ cells but that δ cells also have intrinsic control. The contribution of these cells to overall glucose homeostasis and diabetes onset and progression is still unclear. However, they regulate both α and β cells, both of which are dysfunctional in diabetes, and their numbers are disrupted in humans with diabetes and in multiple animal models of diabetes, suggesting δ cells are a pivotal character in both health and disease.

The pancreas is a dual-function organ, with exocrine cells that aid in digestion and endocrine cells that regulate glucose homeostasis. These cell types share common progenitors and arise from the embryonic ducts. Early signaling events in the embryonic ducts shape the neonatal, adolescent, and adult exocrine and endocrine pancreas. This chapter discusses recent advances in the tools used to study the ducts and our current understanding of how ductal development contributes to pancreatic organogenesis.

Maternal nutrition and metabolic health status during pregnancy are critical factors that shape the life-long health trajectory of offspring. Altered nutrition during specific times of development in utero can lead to functional changes in tissues such as the pancreatic β-cells, predisposing those tissues to metabolic diseases and Type 2 diabetes that manifest later in life. This chapter will focus on the role of pregnancy complications with altered nutrition during gestation in the maladaptive programming of β-cell mass and function in the offspring.

DNA damage poses a significant challenge to all eukaryotic cells, leading to mutagenesis, genome instability and senescence. In somatic cells, the failure to repair damaged DNA can lead to cancer development, whereas, in oocytes, it can lead to ovarian dysfunction and infertility. The response of the cell to DNA damage entails a series of sequential and orchestrated events including sensing the DNA damage, activating DNA damage checkpoint, chromatin-related conformational changes, activating the DNA damage repair machinery and/or initiating the apoptotic cascade. This chapter focuses on how somatic cells and mammalian oocytes respond to DNA damage. Specifically, we will discuss how and why fully grown mammalian oocytes differ drastically from somatic cells and growing oocytes in their response to DNA damage.

Cancer is a global public health issue and remains one of the leading causes of death in the United States (Siegel et al. CA Cancer J Clin. 72:7-33, 2022). It is estimated in the US in 2022, about 935,000 new cases of cancer will be diagnosed in women, and the probability of developing invasive cancer is 5.8% for females younger than 50 years old (Siegel et al. CA Cancer J Clin. 72:7-33, 2022). However, advances in screening programs, diagnostic methods, and therapeutic options have greatly increased the five-year survival rate in reproductive-age women with a variety of cancers. Given the clinical consequences of gonadotoxic cancer therapies, young, female cancer survivors may face compromised fertility, premature ovarian insufficiency, early-onset menopause, and endocrine dysregulation (Bedoschi et al. Future Oncol. 12:2333-44, 2016). Gonadotoxic side effects may include decreased oocyte quality within surviving follicles, loss of ovarian follicles, and impaired ovarian function. In reproductive-age women, oocyte quality is an important element for successful clinical pregnancies and healthy offspring as poor-quality oocytes may be a cause of infertility (McClam et al. Biol Reprod. 106:328-37, 2022; Marteil et al. Reprod Biol. 9:203-24, 2009; Krisher. J Anim Sci. 82: E14-E23, 2004). Thus, it is critical to determine the quantity and quality of surviving follicles in the ovary after cancer treatment and to assess oocyte quality within those surviving follicles as these are markers for determining the capacity for ovarian function restoration and future fertility, especially for young cancer survivors (Xu et al. Nat Med. 17:1562-3, 2011). The long-term effects of cancer therapeutics on oocyte quality are influenced by factors including, but not limited to, individual patient characteristics (e.g. age, health history, comorbidities, etc.), disease type, or treatment regimen (Marci et al. Reprod Biol Endocrinol. 16:1-112, 2018). These effects may translate clinically into an impaired production of viable oocytes and compromised fertility (Garutti et al. ESMO Open. 6:100276, 2021).

Emerging evidence shows that the carotid body (CB) dysfunction is implicated in various physiological and pathophysiological conditions. It has been revealed that the CB structure and neurochemical profile alter in certain human sympathetic-related and cardiometabolic diseases. Specifically, a tiny CB with a decrease of glomus cells and their dense-cored vesicles has been seen in subjects with sleep disordered breathing such as sudden infant death syndrome and obstructive sleep apnea patients and people with congenital central hypoventilation syndrome. Moreover, the CB degranulation is accompanied by significantly elevated levels of catecholamines and proinflammatory cytokines in such patients. The intermittent hypoxia stimulates the CB, eliciting augmented chemoreflex drive and enhanced cardiorespiratory and sympathetic responses. High CB excitability due to blood flow restrictions, oxidative stress, alterations in neurotransmitter gases and disruptions of local mediators is also observed in congestive heart failure conditions. On the other hand, the morpho-chemical changes in hypertension include an increase in the CB volume due to vasodilation, altered transmitter phenotype of chemoreceptor cells and elevated production of neurotrophic factors. Accordingly, in both humans and animal models CB denervation prevents the breathing instability and lowers blood pressure. Knowledge of the morphofunctional aspects of the CB, a better understanding of its role in disease and recent advances in human CB translational research would contribute to the development of new therapeutic strategies.

Over the last century, the structure of the mammalian carotid body (CB) has repeatedly been studied, and our present understanding of its normal morphology is comprehensive. It has been demonstrated that the CB has an intricate internal structure and a remarkable ability to release a wide variety of neurotransmitters and neuromodulators in response to different chemical stimuli. The advances in modern cellular/molecular biological methods and newly developed single-cell electrophysiological techniques have provided an additional insight into the precise working mechanisms and roles of the CB in health and disease. Emerging experimental evidence has also shown that the CB exhibits an extraordinary structural and functional plasticity as a consequence of various environmental stimuli. Lately, the CB has attracted much clinical interest because its dysfunction relates to a number of cardiovascular and respiratory disorders. Expanding knowledge about the pathophysiological mechanisms that alter the CB cell function would certainly help to facilitate the translational research. Recent progress in cell fate experiments has further revealed that the CB is a neurogenic center with a functionally active germinal niche. This may lead to the development of promising new candidate therapies to combat these diseases and improve the quality of human life. Thus, the CB has entered the twenty-first century with its actual designation.

Accumulating evidence suggests that the mammalian carotid body (CB) constitutes a neurogenic center that contains a functionally active germinal niche. A variety of transcription factors is required for the generation of a precursor cell pool in the developing CB. Most of them are later silenced in their progeny, thus allowing for the maturation of the differentiated neurons. In the adult CB, neurotransmitters and vascular cytokines released by glomus cells upon exposure to chronic hypoxia act as paracrine signals that induce proliferation and differentiation of pluripotent stem cells, neuronal and vascular progenitors. Key proliferation markers such as Ki-67 and BrdU are widely used to evaluate the proliferative status of the CB parenchymal cells in the initial phase of this neurogenesis. During hypoxia sustentacular cells which are dormant cells in normoxic conditions can proliferate and differentiate into new glomus cells. However, more recent data have revealed that the majority of the newly formed glomus cells is derived from the glomus cell lineage itself. The mature glomus cells express numerous trophic and growth factors, and their corresponding receptors, which act on CB cell populations in autocrine or paracrine ways. Some of them initially serve as target-derived survival factors and then as signaling molecules in developing vascular targets. Morphofunctional insights into the cellular interactions in the CB stem cell microenvironment can be helpful in further understanding the therapeutic potential of the CB cell niche.