Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis
Abstract Ex vivo expansion of hematopoietic stem cells (HSC) requires the maintenance of a stemness state while cells are proliferating. This can be achieved via exposure to UM171 which leads to the degradation of chromatin modifiers and prevents the loss of key epigenetic marks. However, the chroma...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55225-7 |
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| author | Patrick Coulombe Elisa Tomellini Jalila Chagraoui Nadine Mayotte Guy Sauvageau |
| author_facet | Patrick Coulombe Elisa Tomellini Jalila Chagraoui Nadine Mayotte Guy Sauvageau |
| author_sort | Patrick Coulombe |
| collection | DOAJ |
| description | Abstract Ex vivo expansion of hematopoietic stem cells (HSC) requires the maintenance of a stemness state while cells are proliferating. This can be achieved via exposure to UM171 which leads to the degradation of chromatin modifiers and prevents the loss of key epigenetic marks. However, the chromatin landscape varies across populations within the hematopoietic system and the effect of UM171 on self-renewal and differentiation potential of different hematopoietic progenitor cells is less characterized. To address this, we use the CellTag barcoding approach to track the fate of individual stem and progenitor cells during in vitro expansion. We show that, in addition to its HSC self-renewing property, UM171 specifically modulates cell fate of a precursor common to erythroid, megakaryocytic, and mast cells in favor of self-renewal and a mast-bias differentiation trajectory. This differentiation bias can be driven by pro-inflammatory signaling pathways that are activated downstream of UM171 and results in an abundant mast cell population that can be transplanted as part of the graft to populate mice tissues in xenotransplantation studies. |
| format | Article |
| id | doaj-art-c1e7c0b6559f426896aa7cfa915f868f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c1e7c0b6559f426896aa7cfa915f868f2025-01-05T12:38:52ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-55225-7Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysisPatrick Coulombe0Elisa Tomellini1Jalila Chagraoui2Nadine Mayotte3Guy Sauvageau4Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of MontrealMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of MontrealMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of MontrealMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of MontrealMolecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer (IRIC), University of MontrealAbstract Ex vivo expansion of hematopoietic stem cells (HSC) requires the maintenance of a stemness state while cells are proliferating. This can be achieved via exposure to UM171 which leads to the degradation of chromatin modifiers and prevents the loss of key epigenetic marks. However, the chromatin landscape varies across populations within the hematopoietic system and the effect of UM171 on self-renewal and differentiation potential of different hematopoietic progenitor cells is less characterized. To address this, we use the CellTag barcoding approach to track the fate of individual stem and progenitor cells during in vitro expansion. We show that, in addition to its HSC self-renewing property, UM171 specifically modulates cell fate of a precursor common to erythroid, megakaryocytic, and mast cells in favor of self-renewal and a mast-bias differentiation trajectory. This differentiation bias can be driven by pro-inflammatory signaling pathways that are activated downstream of UM171 and results in an abundant mast cell population that can be transplanted as part of the graft to populate mice tissues in xenotransplantation studies.https://doi.org/10.1038/s41467-024-55225-7 |
| spellingShingle | Patrick Coulombe Elisa Tomellini Jalila Chagraoui Nadine Mayotte Guy Sauvageau Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis Nature Communications |
| title | Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis |
| title_full | Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis |
| title_fullStr | Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis |
| title_full_unstemmed | Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis |
| title_short | Deciphering the effect of UM171 on human hematopoietic progenitor cell fate through clonal analysis |
| title_sort | deciphering the effect of um171 on human hematopoietic progenitor cell fate through clonal analysis |
| url | https://doi.org/10.1038/s41467-024-55225-7 |
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