Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.
Animals ; Chromatin Assembly and Disassembly ; DNA Methylation ; DNA Transposable Elements ; Embryo, Mammalian ; Embryonic Development/genetics* ; Epigenesis, Genetic ; Epigenome ; Female ; Fertilization/physiology* ; Gene Expression Regulation, Developmental ; Histone Code ; Histones/metabolism* ; Male ; Mice ; Oocytes/metabolism* ; Spermatozoa/metabolism*

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

OBJECTIVE: To study the expressions of the members of HSP110 family in the testis and epididymis of mice at different stages of development and whether they are regulated by hormones. METHODS: The testicular and epididymis tissues of mice at different ages (14, 21, 28, 35, 42, 49, 70, and 90 days after birth, 3 mice at each age) were collected for RT-PCR detection of the expression levels of HSP110 family members. Forty-eight mice were randomized into 3 groups for sham operation, castration, or castration with testosterone injections every other day (starting at 7 days after castration), and at 1, 3, 5, and 7 days after first testosterone injection, the expressions of HSP110 family in the epididymis were detected using RT-PCR. RESULTS: The mRNA expression levels of HSP110 family members underwent obvious variations with the development of the mice: , and expressions in the testicles of the mice first increased and then decreased, and gradually became stable; they also exhibited similar temporal patterns of changes in the epididymis. In the castrated mice, the mRNA expressions of and in the epididymis decreased significantly with the reduction of serum hormone levels ( < 0.05), and became normal after the supplementation of exogenous hormone. CONCLUSIONS The expression levels of HSP110 family are affected by developmental regulation, and the expressions of and are under the regulation by hormones.
Animals ; Epididymis ; growth & development ; Gene Expression Regulation, Developmental ; HSP110 Heat-Shock Proteins ; genetics ; metabolism ; Male ; Mice ; Orchiectomy ; Testis ; growth & development ; Testosterone ; pharmacology

Adiposity ; drug effects ; Animals ; Diethylhexyl Phthalate ; toxicity ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Male ; Maternal Exposure ; Metabolic Diseases ; chemically induced ; PPAR gamma ; genetics ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThe aim of this study was to investigate the ability of Pref-1+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes (MLNs) and the dynamic expression of related chemokines during the development of rat MLNs.

METHODSImmunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy (TEM) was used to observe the changes in ultrastructure of MLNs.

RESULTSCells containing lipid droplets were found in all rat MLNs at embryonic day (E) 18.5, 2 and 6 weeks (w) after birth, and they were similar to fibroblastic reticular cells (FRCs) or follicular dendritic cells (FDCs) under TEM. Pref-1+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1 (P < 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth (P < 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth (P < 0.05).

CONCLUSIONAdipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.

Animals ; Chemokines ; genetics ; metabolism ; Female ; Gene Expression Regulation, Developmental ; physiology ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Lymph Nodes ; embryology ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Mesentery ; embryology ; Pregnancy ; Rats

Cardiac valves are highly organized yet delicate structures that ensure unidirectional blood flow through the cardiac chambers and large vessels. Disturbed development of cardiac valves can lead to aberrant heart formation and function which account for approximately one third of congenital heart diseases. The formation of cardiac valves is a dynamic process accomplished by a series of complex events including lineage determination and cell proliferation, differentiation and migration. This paper reviews current knowledge about the role of Tbx20 gene in the development of cardiac valves, which include functional diversities of Tbx20 at various stages of cardiac valve development, its interaction with other signaling pathways, and genetic network involved in endocardial development.
Cell Differentiation ; Cell Proliferation ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Heart Valves ; embryology ; Humans ; T-Box Domain Proteins ; genetics

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Animals ; Animals, Newborn ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Cell Differentiation ; drug effects ; physiology ; Cell Proliferation ; drug effects ; genetics ; Cells, Cultured ; Cuprizone ; toxicity ; Demyelinating Diseases ; chemically induced ; metabolism ; pathology ; Embryo, Mammalian ; Gene Expression Regulation, Developmental ; genetics ; Ki-67 Antigen ; metabolism ; Mice ; Mice, Inbred C57BL ; Myelin Basic Protein ; metabolism ; Myelin Proteolipid Protein ; metabolism ; Myelin Sheath ; drug effects ; metabolism ; Oligodendroglia ; drug effects ; metabolism ; Protein-Tyrosine Kinases ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: : To observe the expression of gene in the early development stage of wild zebrafish embryos. METHODS: : The collinearity of gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of gene in different development stages of zebrafish embryos was detected by hybridization. The -EGFP-pCS recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method. RESULTS: : The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of hybridization showed that the gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of -EGFP-pCS recombinant plasmid were consistent with the results of hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(>0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (>0.05). CONCLUSIONS : The study has observed the expression of gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.
Animals ; Embryo, Nonmammalian ; Gene Expression Regulation, Developmental ; Glucosephosphate Dehydrogenase ; genetics ; Humans ; In Situ Hybridization ; Mice ; Plasmids ; genetics ; Zebrafish ; embryology ; genetics

To clarify the functions and mechanism of stimulated by retinoic acid gene 8 (Stra8) in spermatogenesis, we analyzed the testes from Stra8 knockout and wild-type mice during the first wave of spermatogenesis. Comparisons showed no significant differences in morphology and number of germ cells at 11 days postpartum, while 21 differentially expressed genes (DEGs) associated with spermatogenesis were identified. We speculate that Stra8 performs many functions in different phases of spermatogenesis, such as establishment of spermatogonial stem cells, spermatogonial proliferation and self-renewal, spermatogonial differentiation and meiosis, through direct or indirect regulation of these DEGs. We therefore established a preliminary regulatory network of Stra8 during spermatogenesis. These results will provide a theoretical basis for further research on the mechanism underlying the role of Stra8 in spermatogenesis.
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Cell Proliferation/genetics* ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Male ; Mice ; Mice, Knockout ; Spermatogenesis/genetics* ; Spermatogonia/metabolism* ; Testis/metabolism*

Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life. This study was aimed to investigate the effects of lead exposure of pregnant mice on the expressions of insulin-degrading enzyme (IDE) and nerve growth factor (NGF) in the hippocampus of their offspring. Blood samples were collected from the tail vein, and after anesthetizing the pups, the brain was excised on postnatal day 21. Lead concentrations were determined by graphite furnace atomic absorption spectrophotometry, and the expressions of IDE and NGF were determined by immunohistochemistry and Western blotting. Results showed that the reduction in IDE and NGF expression in the hippocampus of pups might be associated with impairment of learning and memory and dementia induced by maternal lead exposure during pregnancy and lactation.
Animals ; Down-Regulation ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Gene Expression Regulation, Enzymologic ; drug effects ; Hippocampus ; drug effects ; growth & development ; metabolism ; Insulysin ; genetics ; metabolism ; Lead ; toxicity ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced