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The placenta is a chimeric organ containing both maternal and fetal structures (Figure 1). This feat is accomplished by a massive increase in placental transport capacity due saffron a diverse set of developmental processes, including branching and nonbranching angiogenesis, branching morphogenesis, and trophoblast differentiation into several cell types, including invasive cytotrophoblasts (iCTBs) and multinucleated syncytiotrophoblasts (SynTs).

The bulk of our knowledge cabaser pfizer the development of the human placenta stems from analysis of this organ following pregnancy termination or premature delivery. Additionally, animal models cabaser pfizer as the mouse have proven invaluable for deciphering the molecular mechanisms responsible for placentation cabaser pfizer well as the earliest events in establishing cabaser pfizer trophoblast lineage.

Comparative anatomy of human and mouse placentas. Beneath lies a progenitor population cabaser pfizer mononuclear vCTB. At the uterine wall, iCTBs differentiate along the invasive pathway to form anchoring cabaser pfizer (AV). A subset of iCTBs breaches spiral arterioles and differentiates into an endovascular subtype that replaces cabaser pfizer resident maternal endothelium (not shown).

A great deal is known about the many determinants that specify trophoblast cabaser pfizer and placental development. Here we concentrate specifically on the intersection between transcriptional, epigenetic, and physiological factors in specifying placental cell fate.

Pregnancy complications such as preeclampsia and intrauterine growth restriction are thought to arise, xofigo least in part, from aberrations of transcriptional responses to physiological stimuli such as hypoxia (14). Additionally, fetal programming mechanisms depend on the interplay of transcriptional and epigenetic regulators with environmental cues to induce alterations that manifest as disease susceptibility in cabaser pfizer (15).

In this context, a greater understanding of the integrating mechanisms will yield important insights into how this newly appreciated phenomenon translates into clinical pathology during adulthood. Early lineage restriction within the blastocyst. In mice, establishment of the extraembryonic lineages is considered the first differentiation step during early cabaser pfizer development. Following compaction (an increase in intercellular adhesion that causes all the cells to adopt a more flattened morphology), two distinct cell populations are created.

The outer layer, termed the trophectoderm (TE), exhibits features of polarized epithelia, with apical microvilli and the asymmetric distribution of tight and adherens junctions (Figure 2). The component cells give rise to the placenta (reviewed in ref. An underlying aggregate of irregular nonpolarized cells forms the inner cell mass (ICM).

TE cells in direct contact with the ICM, the polar TE, give rise to trophoblast stem (TS) cells in vitro and populate the major structures of the placenta in vivo (Figure 2). The ICM ultimately gives rise to multigen embryo cabaser pfizer (in vivo) or ES cells cabaser pfizer vitro).

This list is not likely to be exhaustive because various sets of transcription factors can induce pluripotency in differentiated cell types (22). Lineage segregation within the mouse blastocyst and early placenta.

TE cells not in direct contact with the ICM form the mural TE, whereas those adjacent to the ICM form the polar TE. The polar TE gives rise to the ExE, from which TS cells can be derived in vitro. Cells within the polar TE continue to proliferate and populate the ExE. Cells within the ExE then differentiate to form the chorionic plate and the EPC.

Transcriptional and epigenetic regulation of trophoblast lineage restriction in the mouse. Critical transcriptional regulators are highlighted in green, and epigenetic cg 60 are highlighted in blue. Undifferentiated ES cells are depicted on the left along with known transcriptional and epigenetic regulators responsible for the maintenance of stemness in mouse ES cells. TS cells are depicted on the right along with the differentiation pathways that give rise to lineage-committed progenitors (CTs and SpTs) as well as the terminally differentiated cells of the placenta (multinucleated SynTs and TGCs).

The factors necessary for the derivation or maintenance of TS cells are indicated along with cabaser pfizer that operate in a lineage- and stage-specific manner. Extraembryonic development also depends cabaser pfizer a unique subset of transcriptional regulators (Figure 3).



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