Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis

  • Amir Giladi
  • Franziska Paul
  • Yoni Herzog
  • Yaniv Lubling
  • Assaf Weiner
  • Ido Yofe
  • Diego Jaitin
  • Nina Cabezas-Wallscheid
  • Regine Dress
  • Florent Ginhoux
  • Andreas Trumpp
  • Amos Tanay
  • Ido Amit

Abstract

The dynamics of haematopoietic stem cell differentiation and the hierarchy of oligopotent stem cells in the bone marrow remain controversial. Here we dissect haematopoietic progenitor populations at single cell resolution, deriving an unbiased reference model of transcriptional states in normal and perturbed murine bone marrow. We define the signature of the naive haematopoietic stem cell and find a continuum of core progenitor states. Core cell populations mix transcription of pre-myeloid and pre-lymphoid programs, but do not mix erythroid or megakaryocyte programs with other fates. CRISP-seq perturbation analysis confirms our models and reveals that Cebpa regulates entry into all myeloid fates, while Irf8 and PU.1 deficiency block later differentiation towards monocyte or granulocyte fates. Our transcriptional map defines a reference network model for blood progenitors and their differentiation trajectories during normal and perturbed haematopoiesis.

Bibliografische Daten

OriginalspracheEnglisch
ISSN1465-7392
DOIs
StatusVeröffentlicht - 2018
Extern publiziertJa
PubMed 29915358