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Related Concept Videos

Embryonic Stem Cells00:58

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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Embryonic Stem Cells00:57

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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
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Research Resource: The Dexamethasone Transcriptome in Hypothalamic Embryonic Neural Stem Cells.

Krystle A Frahm1, Melanie E Peffer1, Janie Y Zhang1

  • 1Department of Pharmacology and Chemical Biology (K.A.F., J.Y.Z., D.B.D.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Program in Integrative Molecular Biology (M.E.P., D.B.D.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biomedical Informatics (S.L., A.B.C., U.R.C.), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology and Molecular Genetics (M.B.C.), Oklahoma State University, Stillwater, Oklahoma; and Department of Neurobiology (A.P.M.), University of Pittsburgh, Pittsburgh, Pennsylvania.

Molecular Endocrinology (Baltimore, Md.)
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Prenatal glucocorticoid exposure impacts offspring stress responses. This study identifies glucocorticoid-regulated genes in developing hypothalamic stem cells, revealing mechanisms for long-term effects.

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Differentiation and Characterization of Neural Progenitors and Neurons from Mouse Embryonic Stem Cells
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Differentiation and Characterization of Neural Progenitors and Neurons from Mouse Embryonic Stem Cells

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Endocrinology

Background:

  • Prenatal exposure to excess glucocorticoids causes lasting effects on offspring physiology and behavior.
  • The developing hypothalamus is implicated as a target for adverse prenatal glucocorticoid actions, impacting stress responses.
  • Mechanisms underlying these long-term consequences remain poorly understood.

Purpose of the Study:

  • To characterize the glucocorticoid transcriptome in male and female mouse hypothalamic neural-progenitor/stem cells (NPSCs).
  • To identify glucocorticoid receptor (GR)-target genes during hypothalamic development.
  • To investigate the impact of glucocorticoid exposure on NPSC proliferation.

Main Methods:

  • Primary hypothalamic NPSCs were derived from embryonic day 14.5 mouse embryos.
  • NPSCs were treated with dexamethasone (a synthetic glucocorticoid) or vehicle.
  • RNA-Sequencing and bioinformatic analysis were used to identify gene expression changes; bromodeoxyuridine (BrdU) incorporation measured proliferation.

Main Results:

  • Hypothalamic NPSC cultures expressed genes regulating stem cell proliferation and progenitor function.
  • Dexamethasone treatment reduced NPSC proliferation.
  • Both equivalently and sex-specifically regulated GR-target genes were identified, suggesting genetic mediation of sex differences.

Conclusions:

  • This study provides the first characterization of glucocorticoid-regulated pathways in embryonic hypothalamic NPSCs.
  • Identified GR-target genes offer insights into mechanisms linking fetal glucocorticoid exposure to adult consequences.
  • Findings highlight the role of hypothalamic development in mediating long-term effects of prenatal stress.