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Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis
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Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis
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Journal Article
Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis
2018
Overview
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.
Using a multi-tier scRNA-seq and CRISP-seq approach, Giladi et al. define a transcriptional signature for the naive haematopoietic stem cell state, and follow progenitor plasticity and fate commitment under the influence of cytokines and growth factors.
