title: Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level.
abstract: Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate that the developmental decline in regenerative potential represents a reversible HSC state.
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Trine A
authors.initials: TA
authors.lastname: Kristiansen
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Jaensson Gyllenbäck
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Alya
authors.initials: A
authors.lastname: Zriwil
authors.affiliation: Molecular Neuromodulation, Department of Experimental Medical Science, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Björklund
authors.affiliation: Chromatin Structure and Function Group, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Daniel
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: Shamit
authors.initials: S
authors.lastname: Soneji
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.affiliation: Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund 22242, Sweden. Electronic address: joan.yuan@med.lu.se.
authors.forename: Joan
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D000066670:Cell Plasticity; D000066673:Cell Self Renewal; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D016130:Immunophenotyping; D008099:Liver / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins; D059010:Single-Cell Analysis
chemical_list: D004268:DNA-Binding Proteins; C570876:Lin28b protein, mouse; D016601:RNA-Binding Proteins