Cadherin-dependent adhesion is required for muscle stem cell niche anchorage and maintenance.

Adhesion between stem cells and their niche provides stable anchorage and signaling cues to sustain properties such as quiescence. Skeletal muscle stem cells (MuSCs) adhere to an adjacent myofiber via cadherin-catenin complexes. Previous studies on N- and M-cadherin in MuSCs revealed that although N-cadherin is required for quiescence, they are collectively dispensable for MuSC niche localization and regenerative activity.

The muscle stem cell niche at a glance.

Skeletal muscle stem cells (MuSCs, also called satellite cells) are the source of the robust regenerative capability of this tissue. The hallmark property of MuSCs at homeostasis is quiescence, a reversible state of cell cycle arrest required for long-term preservation of the stem cell population. MuSCs reside between an individual myofiber and an enwrapping basal lamina, defining the immediate MuSC niche.

Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.

The combination of EGF, CHIR99021, A83-01, SB431542, VPA, and Y27632 (EGF/CASVY) facilitates the derivation of trophoblast stem (TS) cells from human blastocysts and first-trimester, but not term, cytotrophoblasts. The mechanism underlying this chemical induction of TS cells remains elusive. Here we demonstrate that the induction efficiency of cytotrophoblast is determined by functional antagonism of the placental transcription factor GCM1 and the stemness regulator ΔNp63α.

Concepts in Multifactorial Etiology of Developmental Disorders: Gene-Gene and Gene-Environment Interactions in Holoprosencephaly.

Many common developmental disorders are thought to arise from a complex set of genetic and environmental risk factors. These factors interact with each other to affect the strength and duration of key developmental signaling pathways, thereby increasing the possibility that they fail to achieve the thresholds required for normal embryonic patterning. One such disorder, holoprosencephaly (HPE), serves as a useful model system in understanding various forms of multifactorial etiology.

Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development.

Many developmental disorders are thought to arise from an interaction between genetic and environmental risk factors. The Hedgehog (HH) signaling pathway regulates myriad developmental processes, and pathway inhibition is associated with birth defects, including holoprosencephaly (HPE). Cannabinoids are HH pathway inhibitors, but little is known of their effects on HH-dependent processes in mammalian embryos, and their mechanism of action is unclear.

Ferritin RNA interference inhibits the formation of iron granules in the trophocytes of worker honey bees (Apis mellifera).

Iron granules containing superparamagnetic magnetite act as magnetoreceptor for magnetoreception in honey bees. Biomineralization of iron granules occurs in the iron deposition vesicles of trophocytes and requires the participation of actin, myosin, ferritin2, and ATP synthase. The mechanism of magnetoreception in honey bees can be explored by suppressing the formation of iron granules.

SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1-WNT10B-FZD7 axis.

Migration of placental extravillous trophoblast (EVT) cells into uterine decidua facilitates the establishment of blood circulation between mother and fetus and is modulated by EVT-decidual cell interaction. Poor or excessive EVT migration is associated with pregnancy complications such as preeclampsia or placenta accreta. Glial cells missing 1 (GCM1) transcription factor is essential for placental development, and decreased GCM1 activity is detected in preeclampsia.

Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion.

The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with pre-eclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion.

A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.

Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation.

Functional antagonism between high temperature requirement protein A (HtrA) family members regulates trophoblast invasion.

Human trophoblast invasion of decidualized endometrium is essential for placentation and is tightly regulated and involves trophoblast-decidual cell interaction. High temperature requirement A4 (HtrA4) is a secreted serine protease highly expressed in the invasive extravillous trophoblasts that invade decidua. In contrast, both HtrA1 and HtrA3 have been shown to inhibit trophoblast invasion.

RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion.

GCM1 (glial cell missing 1) is a short-lived transcription factor essential for placental development. The F-box protein, FBW2 (F-box and WD-repeat domain-containing 2), which contains five WD (tryptophan-aspartate) repeats, recognizes GCM1 and mediates its ubiquitination via the SCFFBW2 E3 ligase complex. Although the interaction between GCM1 and FBW2 is facilitated by GCM1 phosphorylation, it is possible that this interaction might be regulated by additional cellular factors.

Caspase-14 suppresses GCM1 acetylation and inhibits placental cell differentiation.

Glial cell missing 1 (GCM1) transcription factor regulates placental cell fusion into the syncytiotrophoblast. Caspase-14 is proteolytically activated to mediate filaggrin processing during keratinocyte differentiation. Interestingly, altered expression of nonactivated caspase-14 proenzyme is associated with tumorigenesis and diabetic retinopathy, suggesting that caspase-14 may perform physiological functions independently of its protease activity.

Molecular interaction between caveolin-1 and ABCA1 on high-density lipoprotein-mediated cholesterol efflux in aortic endothelial cells.

Objective: Caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) are proteins that are involved in cellular cholesterol efflux. In this study, we analyzed the relationships between caveolin-1 and ABCA1 on high-density lipoprotein (HDL)-mediated cholesterol efflux in rat aortic endothelial cells.

Methods And Results: Overexpression of caveolin-1 by transfection with caveolin-1 cDNA in aortic endothelial cells up-regulated ABCA1 expression and enhanced cholesterol efflux.