Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells
Summary: The process of hematopoiesis is subject to substantial ontogenic remodeling that is accompanied by alterations in cellular fate during both development and disease. We combine state-of-the-art mass spectrometry with extensive functional assays to gain insight into ontogeny-specific proteomi...
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doaj-cf5b5f27760c4796b3e9796e54bf9bee2021-03-25T04:28:51ZengElsevierCell Reports2211-12472021-03-013412108894Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cellsMaria Jassinskaja0Kristýna Pimková1Nejc Arh2Emil Johansson3Mina Davoudi4Carlos-Filipe Pereira5Ewa Sitnicka6Jenny Hansson7Lund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Medicine and Gene Therapy, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, Sweden; Department of Laboratory Medicine, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Medicine and Gene Therapy, Lund University, 221 84 Lund, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, SwedenLund Stem Cell Center, Division of Molecular Hematology, Lund University, 221 84 Lund, Sweden; Corresponding authorSummary: The process of hematopoiesis is subject to substantial ontogenic remodeling that is accompanied by alterations in cellular fate during both development and disease. We combine state-of-the-art mass spectrometry with extensive functional assays to gain insight into ontogeny-specific proteomic mechanisms regulating hematopoiesis. Through deep coverage of the cellular proteome of fetal and adult lympho-myeloid multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs), and granulocyte-monocyte progenitors (GMPs), we establish that features traditionally attributed to adult hematopoiesis are conserved across lymphoid and myeloid lineages, whereas generic fetal features are suppressed in GMPs. We reveal molecular and functional evidence for a diminished granulocyte differentiation capacity in fetal LMPPs and GMPs relative to their adult counterparts. Our data indicate an ontogeny-specific requirement of myosin activity for myelopoiesis in LMPPs. Finally, we uncover an ontogenic shift in the monocytic differentiation capacity of GMPs, partially driven by a differential expression of Irf8 during fetal and adult life.http://www.sciencedirect.com/science/article/pii/S2211124721002084fetal hematopoiesisadult hematopoiesisproteomicshematopoietic progenitor cellslymphopoiesismyelopoiesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Jassinskaja Kristýna Pimková Nejc Arh Emil Johansson Mina Davoudi Carlos-Filipe Pereira Ewa Sitnicka Jenny Hansson |
spellingShingle |
Maria Jassinskaja Kristýna Pimková Nejc Arh Emil Johansson Mina Davoudi Carlos-Filipe Pereira Ewa Sitnicka Jenny Hansson Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells Cell Reports fetal hematopoiesis adult hematopoiesis proteomics hematopoietic progenitor cells lymphopoiesis myelopoiesis |
author_facet |
Maria Jassinskaja Kristýna Pimková Nejc Arh Emil Johansson Mina Davoudi Carlos-Filipe Pereira Ewa Sitnicka Jenny Hansson |
author_sort |
Maria Jassinskaja |
title |
Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
title_short |
Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
title_full |
Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
title_fullStr |
Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
title_full_unstemmed |
Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
title_sort |
ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-03-01 |
description |
Summary: The process of hematopoiesis is subject to substantial ontogenic remodeling that is accompanied by alterations in cellular fate during both development and disease. We combine state-of-the-art mass spectrometry with extensive functional assays to gain insight into ontogeny-specific proteomic mechanisms regulating hematopoiesis. Through deep coverage of the cellular proteome of fetal and adult lympho-myeloid multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs), and granulocyte-monocyte progenitors (GMPs), we establish that features traditionally attributed to adult hematopoiesis are conserved across lymphoid and myeloid lineages, whereas generic fetal features are suppressed in GMPs. We reveal molecular and functional evidence for a diminished granulocyte differentiation capacity in fetal LMPPs and GMPs relative to their adult counterparts. Our data indicate an ontogeny-specific requirement of myosin activity for myelopoiesis in LMPPs. Finally, we uncover an ontogenic shift in the monocytic differentiation capacity of GMPs, partially driven by a differential expression of Irf8 during fetal and adult life. |
topic |
fetal hematopoiesis adult hematopoiesis proteomics hematopoietic progenitor cells lymphopoiesis myelopoiesis |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721002084 |
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