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| Status |
Public on Feb 21, 2018 |
| Title |
Population snapshots predict early haematopoietic and erythroid hierarchies |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots, to demonstrate that mouse hematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.
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| Overall design |
Single-cell mRNA sequencing of hematopoietic progenitors from mouse bone marrow and fetal liver.
Sample Bone marrow, basal: 5432 single cells.
Sample Bone marrow, Epo-stimulated: 2954 single cells.
Sample Fetal liver: 9482 single cells.
Sample P1: 3104 single cells.
Sample P1-CD71hi: 752 single cells.
Sample P2: 2435 single cells.
Sample P3: 2032 single cells.
Sample P4: 1210 single cells.
Sample P5: 2460 single cells.
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| Contributor(s) |
Khoramian Tusi B, Wolock SL, Weinreb C, Hwang Y, Hidalgo D, Zilionis R, Waisman A, Huh JR, Klein AM, Socolovsky M |
| Citation(s) |
29466336, 29463712 |
| Submission date |
Nov 10, 2016 |
| Last update date |
Aug 26, 2019 |
| Contact name |
Merav Socolovsky |
| E-mail(s) |
Merav.Socolovsky@umassmed.edu
|
| Organization name |
University of Massachusetts Medical School
|
| Department |
Molecular, Cell and Cancer Biology
|
| Street address |
364 Plantation St
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01605 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA353098 |
| SRA |
SRP093236 |
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