StemTherapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
Göran Karlsson
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden; StemTherapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
Joan Yuan
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden; StemTherapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
Shamit Soneji
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden; StemTherapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden
Pankaj K Mandal
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children’s Hospital, Massachusetts, United States
Derrick J Rossi
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States; Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children’s Hospital, Massachusetts, United States
Division of Molecular Hematology, Department of Laboratory Medicine, Medical Faculty, Lund University, Lund, Sweden; StemTherapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden
A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.
