Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis

Research output: Contribution to journalResearch articleContributedpeer-review



Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48 hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48 −/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis.


Original languageEnglish
Article number4504
JournalNature communications
Early online date3 Aug 2022
Publication statusPublished - Dec 2022

External IDs

Scopus 85135341156
PubMed 35922411
WOS 000835788400023
Mendeley 5258789f-230e-36c0-bcd2-4de8b53c0d16
unpaywall 10.1038/s41467-022-31914-z


DFG Classification of Subject Areas according to Review Boards

Subject groups, research areas, subject areas according to Destatis


  • Cell Differentiation/physiology, Cell Lineage, Hematopoietic Stem Cells/metabolism, Myelopoiesis, Thrombopoiesis/physiology