title: The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis.
abstract: Long-term repopulating (LT) hematopoietic stem cells (HSCs) are the most undifferentiated cells at the top of the hematopoietic hierarchy. The regulation of HSC pool size and its contribution to hematopoiesis are incompletely understood. We depleted hematopoietic stem and progenitor cells (HSPCs) in adult mice in situ and found that LT-HSCs recovered from initially very low levels (<1%) to below 10% of normal numbers but not more, whereas progenitor cells substantially recovered shortly after depletion. In spite of the persistent and massive reduction of LT-HSCs, steady-state hematopoiesis was unaffected and residual HSCs remained quiescent. Hematopoietic stress, although reported to recruit quiescent HSCs into cycle, was well tolerated by HSPC-depleted mice and did not induce expansion of the small LT-HSC compartment. Only upon 5-fluorouracil treatment was HSPC-depleted bone marrow compromised in reconstituting hematopoiesis, demonstrating that HSCs and early progenitors are crucial to compensate myeloablation. Hence, a contracted HSC compartment cannot recover in situ to its original size, and normal steady-state blood cell generation is sustained with <10% of normal LT-HSC numbers without increased contribution of the few residual cells.
authors.affiliation: Institute for Immunology.
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Schoedel
authors.affiliation: Institute for Immunology.
authors.forename: Mina N F
authors.initials: MNF
authors.lastname: Morcos
authors.affiliation: Institute for Medical Informatics and Biometry, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zerjatke
authors.affiliation: Institute for Medical Informatics and Biometry, and.
authors.forename: Ingo
authors.initials: I
authors.lastname: Roeder
authors.affiliation: Department for Clinical Pathobiochemistry, Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Grinenko
authors.affiliation: Department of Infection Biology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.affiliation: Department of Hematology, University Hospital of Essen, Essen, Germany; and.
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Göthert
authors.affiliation: Regeneration in Hematopoiesis, Institute for Immunology, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
authors.affiliation: Institute for Immunology.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.affiliation: Institute for Immunology.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerbaulet
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche; D013312:Stress, Physiological