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Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells

Jassinskaja, Maria LU ; Pimková, Kristýna LU ; Arh, Nejc LU orcid ; Johansson, Emil LU orcid ; Davoudi, Mina LU orcid ; Pereira, Carlos Filipe LU orcid ; Sitnicka, Ewa LU and Hansson, Jenny LU orcid (2021) In Cell Reports 34(12).
Abstract

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... (More)

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.

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organization
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Contribution to journal
publication status
published
subject
keywords
Adult Stem Cells/cytology, Animals, Cell Differentiation, Cell Lineage, Fetus/cytology, Granulocytes/cytology, HEK293 Cells, Hematopoietic Stem Cells/cytology, Humans, Immunophenotyping, Interferon Regulatory Factors/metabolism, Kinetics, Lymphoid Progenitor Cells/cytology, Mice, Inbred C57BL, Monocytes/cytology, Myeloid Progenitor Cells/cytology, Proteome/metabolism, Proteomics, rho-Associated Kinases/antagonists & inhibitors
in
Cell Reports
volume
34
issue
12
article number
108894
publisher
Cell Press
external identifiers
  • pmid:33761361
  • scopus:85103319786
ISSN
2211-1247
DOI
10.1016/j.celrep.2021.108894
language
English
LU publication?
yes
id
9263af1d-3a97-4561-a63c-2156e282a4cf
date added to LUP
2021-04-07 13:04:11
date last changed
2023-09-12 17:53:29
@article{9263af1d-3a97-4561-a63c-2156e282a4cf,
  abstract     = {{<p>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.</p>}},
  author       = {{Jassinskaja, Maria and Pimková, Kristýna and Arh, Nejc and Johansson, Emil and Davoudi, Mina and Pereira, Carlos Filipe and Sitnicka, Ewa and Hansson, Jenny}},
  issn         = {{2211-1247}},
  keywords     = {{Adult Stem Cells/cytology; Animals; Cell Differentiation; Cell Lineage; Fetus/cytology; Granulocytes/cytology; HEK293 Cells; Hematopoietic Stem Cells/cytology; Humans; Immunophenotyping; Interferon Regulatory Factors/metabolism; Kinetics; Lymphoid Progenitor Cells/cytology; Mice, Inbred C57BL; Monocytes/cytology; Myeloid Progenitor Cells/cytology; Proteome/metabolism; Proteomics; rho-Associated Kinases/antagonists & inhibitors}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Ontogenic shifts in cellular fate are linked to proteotype changes in lineage-biased hematopoietic progenitor cells}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2021.108894}},
  doi          = {{10.1016/j.celrep.2021.108894}},
  volume       = {{34}},
  year         = {{2021}},
}