October 24, 2021

Cell biomarkers in placenta research

Context is important for cell markers. Before you use these markers, consider that KRT7 is a marker for trophoblast cells in placenta, but you would not say that any particular cell is a trophoblast just because it expresses KRT7. It is also a common marker for lung research even though lungs don't have any trophoblasts. That is because KRT7 is generally expressed by epithelial cells, and in placenta those are trophoblasts, but lungs have other epithelial cells. Sample context is important.

Also consider RNA vs protein, localization, and experiment use. Some markers are useful to identify cell types in single cell RNA-seq results because the RNA is specifically or mostly expressed by specific cell types, but the protein is not expressed at the cell surface so you wouldn't use that marker to sort cells for flow cytometry. 

  • KRT7 = CK7 = Cytokeratin 7 = marker for epithelial cells
    • Expressed by all epithelial cells
    • All trophoblast cells in placenta are epithelial, so KRT7 is used as a trophoblast cell marker in placenta tissue
    • qRT-PCR marker
    • Cell surface marker suitable for flow cytometry
    • Beware that fibroblasts also express KRT7 and primary cells in culture will eventually become fibroblast cells
  • CDX2 = marker for early cytotrophoblasts (CTBs)
    • Expressed in CTBs around 6 weeks, but diminishes as 1st trimester progresses (Horii et al 2016).
    • Indicates stem cell-like phenotypes
    • Immunohistochemistry (IHC) and gene expression marker for early cytotrophoblasts

  • CD9 = marker for extravillous trophoblasts (EVTs)
  • CD42b = platelet marker
    • Immunohistochemistry (IHC) marker
    • Used by Guettler et al 2021 to stain maternal platelets at the maternal-fetal interface

  • CD44 = marker for fibroblast cells
    • Used as a negative selection to remove fibroblasts from iPSC mixed populations
    • Immunohistochemistry (IHC) marker

  • CD45 = pan-leukocyte marker
    • Leukocytes are white blood cells. They include neutrophils, basophils, eosinophils, monocytes (dendritic cells and macrophages), lymphocytes, T-cells, and B-cells.
    • Stains Hofbauer cells (fetal macrophages)
    • Immunohistochemistry (IHC) marker

  • CD69 = monocyte/macrophage marker
    • It stains myeloid cells, dendritic cells, Hoefbauer cells, and several other immune cell types.
    • "CD69 is a membrane-bound, type II C-lectin receptor. It is a classical early marker of lymphocyte activation due to its rapid appearance on the surface of the plasma membrane after stimulation. CD69 is expressed by several subsets of tissue resident immune cells, including resident memory T (TRM) cells and gamma delta (γδ) T cells, and is therefore considered a marker of tissue retention." [Cibrián and Sánchez-Madrid 2019]
  • CGB = hCG = marker for syncytiotrophoblasts (STBs)
    • CGB is the gene, use as a qRT-PCR marker
    • hCG is the product, secretion by cells and detected with ELISA

  • CSH1, CSH2 = hPL = human placental lactogen = marker for syncytiotrophoblasts
    • CSH1, CSH2 are the genes. They are very highly expressed in placenta, especially at third trimester.
    • hPL is an ELISA marker for syncytiotrophoblasts, less commonly used than hCG

  • EGFR = marker for cytotrophoblasts (CTBs)
    • Immunohistochemistry (IHC) marker

  • ELF5 = trophoblast stem cell marker in mice
    • Used by Horii et al 2016 for mouse TSCs
    • Human early placenta cells express ELF5 but it "is not expressed in the TE of the human preimplantation blastocyst" (Horii et al 2016

  • HLA-G = marker for extravillous trophoblasts (EVTs)
    • Not expressed by syncytiotrophoblasts or cytotrophoblasts or stem cells, only extravillous trophoblasts
    • qRT-PCR marker
    • Cell surface marker suitable for flow cytometry

  • MMP2, MMP9 = matrix metallopeptidase genes = markers for extravillous trophoblasts
    • Indicate migratory phenotypes
    • Secreted by EVTs, detected with ELISA tests

  • Nanog = stem cell marker
    • Expressed in trophectoderm (TE), the outer layer of the blastocyst that developmentally gives rise to the placenta
    • Involved in embryonic stem cell proliferation, renewal, and pluripotency
    • Blocks cell differentiation

  • p63 = marker for all cytotrophoblasts in early/late gestation 5-20 weeks
  • TEAD4 = marker for cytotrophoblasts
  • Vimentin = marker for mesenchymal cells
    • In placenta, used as a marker for stromal cells
    • Trophoblast cells do not express vimentin 
    • Abou-Kheir et al 2015 looks at term placenta and BeWo cell line
    • Graham et al 1993 - the HTR8/SVneo cell line citation used vimentin as a negative marker (something they didn't want)

Placenta stem cell research articles (suggested reading)


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Last updated 1/31/2024 to add suggested reading.


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