title: Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs.
abstract: Adult hematopoietic stem cells (HSCs) with serially transplantable activity comprise two subtypes. One shows a balanced output of mature lymphoid and myeloid cells; the other appears selectively lymphoid deficient. We now show that both of these HSC subtypes are present in the fetal liver (at a 1:10 ratio) with the rarer, lymphoid-deficient HSCs immediately gaining an increased representation in the fetal bone marrow, suggesting that the marrow niche plays a key role in regulating their ensuing preferential amplification. Clonal analysis of HSC expansion posttransplant showed that both subtypes display an extensive but variable self-renewal activity with occasional interconversion. Clonal analysis of their differentiation programs demonstrated functional and molecular as well as quantitative HSC subtype-specific differences in the lymphoid progenitors they generate but an indistinguishable production of multipotent and myeloid-restricted progenitors. These findings establish a level of heterogeneity in HSC differentiation and expansion control that may have relevance to stem cell populations in other hierarchically organized tissues.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Claudia
authors.initials: C
authors.lastname: Benz
authors.forename: Michael R
authors.initials: MR
authors.lastname: Copley
authors.forename: David G
authors.initials: DG
authors.lastname: Kent
authors.forename: Stefan
authors.initials: S
authors.lastname: Wohrer
authors.forename: Adrian
authors.initials: A
authors.lastname: Cortes
authors.forename: Nima
authors.initials: N
authors.lastname: Aghaeepour
authors.forename: Elaine
authors.initials: E
authors.lastname: Ma
authors.forename: Heidi
authors.initials: H
authors.lastname: Mader
authors.forename: Keegan
authors.initials: K
authors.lastname: Rowe
authors.forename: Christopher
authors.initials: C
authors.lastname: Day
authors.forename: David
authors.initials: D
authors.lastname: Treloar
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D016922:Cellular Senescence; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy