Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals

• DOI: 10.1016/j.immuni.2016.08.007
• Publication Date: 2016-09-09T15:30:59Z
• Authors: Catherine M. Sawai; Sonja Babovic; Samik Upadhaya; David J.H.F. Knapp; Yonit Lavin; Colleen M. Lau; Anton Goloborodko; Jue Feng; Joji Fujisaki; Lei Ding; Leonid A. Mirny; Miriam Merad; Connie J. Eaves; Boris Reizis
• Keywords: Blood Platelets; B-Lymphocytes; 0303 health sciences; Macrophages; Hematopoietic Stem Cell Transplantation; Cell Differentiation; Hematopoietic Stem Cells; Hematopoiesis; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Cell Lineage; Myeloid Cells; Interferons

Hematopoietic stem cells (HSCs) sustain long-term reconstitution of hematopoiesis in transplantation recipients, yet their role in the endogenous steady-state hematopoiesis remains unclear. In particular, recent studies suggested that HSCs provide a relatively minor contribution to immune cell development in adults. We directed transgene expression in a fraction of HSCs that maintained reconstituting activity during serial transplantations. Inducible genetic labeling showed that transgene-expressing HSCs gave rise to other phenotypic HSCs, confirming their top position in the differentiation hierarchy. The labeled HSCs rapidly contributed to committed progenitors of all lineages and to mature myeloid cells and lymphocytes, but not to B-1a cells or tissue macrophages. Importantly, labeled HSCs gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be accelerated by an induced interferon response. Thus, classically defined HSCs maintain immune cell development in the steady state and during systemic cytokine responses.