PUBLICATION

Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2

Authors
Soto, R.A., Najia, M.A.T., Hachimi, M., Frame, J.M., Yette, G.A., Lummertz da Rocha, E., Stankunas, K., Daley, G.Q., North, T.E.
ID
ZDB-PUB-210622-27
Date
2021
Source
Stem Cell Reports   16(7): 1718-1734 (Journal)
Registered Authors
Keywords
Ezh1, Ezh2, endothelial-to-hematopoietic transition (EHT), hematopoiesis, hematopoietic stem/progenitor cell (HSPC), hemogenic endothelium (HE), zebrafish
Datasets
GEO:GSE173972
MeSH Terms
  • Mice
  • Enhancer of Zeste Homolog 2 Protein/metabolism*
  • Zebrafish Proteins/metabolism*
  • RNA-Seq
  • Hematopoiesis
  • Zebrafish/metabolism*
  • Hematopoietic Stem Cells/metabolism*
  • Single-Cell Analysis
  • Embryo, Nonmammalian/metabolism
  • Lymphocytes/metabolism
  • Endothelial Cells/metabolism
  • Gene Knockdown Techniques
  • Loss of Function Mutation
  • Animals
  • Polycomb Repressive Complex 2/metabolism*
  • Hemangioblasts/metabolism*
(all 16)
PubMed
34143974 Full text @ Stem Cell Reports
Abstract
Across species, hematopoietic stem and progenitor cells (HSPCs) arise during embryogenesis from a specialized arterial population, termed hemogenic endothelium. Here, we describe a mechanistic role for the epigenetic regulator, Enhancer of zeste homolog-1 (Ezh1), in vertebrate HSPC production via regulation of hemogenic commitment. Loss of ezh1 in zebrafish embryos favored acquisition of hemogenic (gata2b) and HSPC (runx1) fate at the expense of the arterial program (ephrinb2a, dll4). In contrast, ezh1 overexpression blocked hematopoietic progression via maintenance of arterial gene expression. The related Polycomb group subunit, Ezh2, functioned in a non-redundant, sequential manner, whereby inhibition had no impact on arterial identity, but was capable of blocking ezh1-knockdown-associated HSPC expansion. Single-cell RNA sequencing across ezh1 genotypes revealed a dropout of ezh1+/- cells among arterial endothelium associated with positive regulation of gene transcription. Exploitation of Ezh1/2 modulation has potential functional relevance for improving in vitro HSPC differentiation from induced pluripotent stem cell sources.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
AB + MO1-ezh1standard conditionsPrim-5
1 - 10 of 53
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1394
    		Small Deletion
    fb12TgTransgenic Insertion
      hu5333TgTransgenic Insertion
        la2TgTransgenic Insertion
          la116TgTransgenic Insertion
            mu271TgTransgenic Insertion
              s843TgTransgenic Insertion
                s916TgTransgenic Insertion
                  sd2TgTransgenic Insertion
                    sd32TgTransgenic Insertion
                      1 - 10 of 15
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      ezh1MO1-ezh1MRPHLNO
                      1 - 1 of 1
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                      Fish
                      Fish
                      AB
                      AB + MO1-ezh1
                      ezh1b1394/b1394
                      ezh1b1394/b1394; s843Tg/s843Tg
                      ezh1b1394/+
                      ezh1b1394/+; s843Tg/s843Tg
                      la2Tg/la2Tg
                      la2Tg/la2Tg + MO1-ezh1
                      s843Tg/s843Tg
                      s916Tg/s916Tg; zf169Tg/zf169Tg
                      1 - 10 of 18
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                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-efnb2polyclonalIgGGoat
                      1 - 1 of 1
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                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      KALTA4EFGKALTA4
                      mCherryEFGmCherry
                      RFPEFGRFP
                      1 - 7 of 7
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                      Mapping
                      No data available
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                      Citation
                      Soto, R.A., Najia, M.A.T., Hachimi, M., Frame, J.M., Yette, G.A., Lummertz da Rocha, E., Stankunas, K., Daley, G.Q., North, T.E. (2021) Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2. Stem Cell Reports. 16(7):1718-1734.