Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage.

Autor: Tufa DM; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Shank T; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Yingst AM; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Trahan GD; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Shim S; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Lake J; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Woods R; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Jones K; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA., Verneris MR; University of Colorado and Children's Hospital of Colorado, Department of Pediatrics, Center for Cancer and Blood Disorders. Research Complex 1, North Tower, 12800 E. 19th Ave., Mail Stop 8302, Room P18-4108, Aurora, CO, 80045, USA. Michael.Verneris@CUAnschutz.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Apr 14; Vol. 10 (1), pp. 6335. Date of Electronic Publication: 2020 Apr 14.
DOI: 10.1038/s41598-020-63346-4
Abstrakt: Numerous cell types modulate hematopoiesis through soluble and membrane bound molecules. Whether developing hematopoietic progenitors of a particular lineage modulate the differentiation of other hematopoietic lineages is largely unknown. Here we aimed to investigate the influence of myeloid progenitors on CD34 + cell differentiation into CD56 + innate lymphocytes. Sorted CD34 + cells cultured in the presence of stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand (FLT3L) give rise to numerous cell types, including progenitors that expressed the prolactin receptor (PRLR). These CD34 + PRLR + myeloid-lineage progenitors were derived from granulocyte monocyte precursors (GMPs) and could develop into granulocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Moreover, CD34 + PRLR + myeloid progenitors lacked lymphoid developmental potential, but when stimulated with prolactin (PRL) they increased the differentiation of other CD34 + cell populations into the NK lineage in a non-contact dependent manner. Both mRNA and protein analyses show that PRL increased mothers against decapentaplegic homolog 7 (SMAD7) in CD34 + PRLR + myeloid cells, which reduced the production of transforming growth factor beta 1 (TGF-β1), a cytokine known to inhibit CD56 + cell development. Thus, we uncover an axis whereby CD34 + PRLR + GMPs inhibit CD56 + lineage development through TGF-β1 production and PRL stimulation leads to SMAD7 activation, repression of TGF-β1, resulting in CD56 + cell development.
Databáze: MEDLINE
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