RT Journal Article
SR Electronic
T1 Ontogenic Shifts in Cellular Fate Are Linked to Proteotype Changes in Mouse Hematopoietic Progenitor Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.08.193276
DO 10.1101/2020.07.08.193276
A1 Maria Jassinskaja
A1 Kristýna Pimková
A1 Emil Johansson
A1 Ewa Sitnicka
A1 Jenny Hansson
YR 2020
UL http://biorxiv.org/content/early/2020/07/09/2020.07.08.193276.abstract
AB The process of hematopoiesis is subject to extensive ontogenic remodeling that is accompanied by alterations in cellular fate both during normal development and upon malignant transformation. Although the functional differences between fetal and adult hematopoiesis are well established, the responsible molecular mechanisms have long remained largely unexplored at the proteomic level. Here, we have applied state-of-the-art mass spectrometry to gain deep coverage of the proteome of 100,000 fetal and adult lympho-myeloid multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and granulocyte-monocyte progenitors (GMPs). Our analysis resulted in the identification and quantification of 4189 proteins, with over 200 proteins per cell type displaying differential expression between the fetus and the adult. The proteomic data demonstrate that features traditionally attributed to adult hematopoiesis are conserved across lymphoid and myeloid lineages, while generic fetal features are considerably more prominent in LMPPs and CLPs than in GMPs. Furthermore, we reveal molecular and functional evidence for a diminished granulocyte differentiation capacity in fetal LMPPs and GMPs relative to their adult counterparts, and show indications of a differential requirement of myosin activity for granulopoiesis in fetal and adult LMPPs. We have additionally identified the transcription factor Irf8 as significantly lower expressed in fetal relative to adult GMPs, and shown that its expression pattern correlates with an altered capacity for monocytic differentiation in the fetal cells. Collectively, our work represents a significant advancement in the understanding of the molecular programs that govern ontogenic differences in early hematopoiesis and mature blood cell production.Key pointsIn-depth proteomics links intrinsic molecular programs to functional output of fetal and adult lineage-biased hematopoietic progenitorsMyelopoiesis-associated molecular programs and myeloid differentiation capacity are subject to considerable ontogenic remodelingCompeting Interest StatementThe authors have declared no competing interest.