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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

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.

Details

OriginalspracheEnglisch
Aufsatznummer4504
FachzeitschriftNature communications
Jahrgang13
Frühes Online-Datum3 Aug. 2022
PublikationsstatusVeröffentlicht - Dez. 2022
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

Fächergruppen, Lehr- und Forschungsbereiche, Fachgebiete nach Destatis

Schlagwörter

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

Bibliotheksschlagworte