Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells

Abstract

Significance: Comparing human blood cell types, nuclear diversity is visually striking but unexplained: quasi-spherical nuclei in stem/progenitor cells and T cells contrast with multilobed nuclei in neutrophils, giant nuclei in megakaryocytes, and anuclear erythrocytes. We hypothesized broad roles for the major nuclear structure proteins—lamins—and developed mass spectrometry-calibrated intracellular flow cytometry to quantify lamin-A:B ratios. This ratio controls both nuclear viscoelasticity and cell trafficking across microporous barriers. High A:B rigidifies erythroblast nuclei to favor marrow retention and also enhances erythropoiesis. Intermediate A:B enhances thrombopoiesis and opposes cell division to favor marrow anchorage of megakaryocytes. Human stem/progenitor cells have moderate lamin levels and reside in marrow whereas white cells are favored by low lamins and predominantly circulate.