Genomics,Multiomics

Dataset Information

38

Transcriptional plasticity, priming and commitment in hematopoietic lineages [CRISP-seq]


ABSTRACT: Differentiation of adult hematopoietic stem cells (HSC) constantly produces the cell types of the blood and immune system. The dynamics of this process and the hierarchy of downstream oligopotent stem cell differentiation remain controversial. Here we dissect hematopoietic progenitor populations in a minimally biased fashion using extensive single cell sampling from murine bone marrow. We characterize the HSC population, define its quiescent transcriptional program and validate it with label retaining assays and cytokine mediated stimulations. Analysis of initial HSC commitment defines marked bifurcation of erythroid/megakaryocytic cells from myeloid/lymphoid lineages. Unexpectedly, we find states that mix transcription of pre-myeloid and pre-lymphoid genes. This suggests a model in which more than one differentiation trajectory can link HSC to several cell types. Dendritic cells are thus linked with both monocyte and lymphocyte precursors. Our data support a model of hematopoiesis balancing relaxation of an HSC quiescent state, gradual bifurcations and trans-differentiation. Overall design: Cas9-GFP LSK cells were infected with BFP+ lentiviral guide RNAs and transplanted into irradiated mice. Both mRNA content and matched lentiviral transcribed barcodes were extracted and sequenced in different batches on an Illumina NextSeq

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

ORGANISM(S): Mus musculus  

SUBMITTER: Ido Amit  

PROVIDER: GSE113494 | GEO | 2018-06-19

REPOSITORIES: GEO

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Publications

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

Giladi Amir A   Paul Franziska F   Herzog Yoni Y   Lubling Yaniv Y   Weiner Assaf A   Yofe Ido I   Jaitin Diego D   Cabezas-Wallscheid Nina N   Dress Regine R   Ginhoux Florent F   Trumpp Andreas A   Tanay Amos A   Amit Ido I  

Nature cell biology 20180618 7


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 p  ...[more]

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