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Regulation of Hematopoietic Stem Cells

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...

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Updated: Mar 1, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Published on: October 25, 2018

Reconstructing blood stem cell regulatory network models from single-cell molecular profiles.

Fiona K Hamey¹, Sonia Nestorowa¹, Sarah J Kinston¹

¹Department of Haematology, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America

|June 7, 2017

Summary

This study reveals how transcription factors control blood stem cell differentiation. The new network inference method accurately models cell fate decisions, identifying key regulatory differences in hematopoiesis.

Keywords:

Boolean network gene regulatory networks hematopoiesis single cell stem progenitor cells

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Last Updated: Mar 1, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Published on: October 25, 2018

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Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors

Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors

Published on: November 4, 2019

Area of Science:

Hematopoiesis
Systems Biology
Molecular Biology

Background:

Adult blood comprises diverse mature cell types originating from hematopoietic stem cells (HSCs).
HSC differentiation is tightly regulated by transcription factors within complex networks.
Dysregulation of HSC fate decisions can lead to malignancies like leukemia.

Purpose of the Study:

To develop and apply a network inference method for understanding single HSC fate decisions.
To model transcriptional regulatory networks governing HSC differentiation.
To identify and validate regulatory differences in HSC lineage commitment.

Main Methods:

Inferred dynamic information from single-cell snapshot gene expression data.
Analyzed expression profiles of 48 genes in 2,167 blood stem and progenitor cells.
Developed transcriptional regulatory network models for HSC differentiation trajectories.

Main Results:

Successfully recapitulated HSC differentiation into megakaryocyte-erythrocyte and lymphoid-primed multipotent progenitors.
Identified and experimentally validated differential regulation of Nfe2 and Cbfa2t3h by Gata2.
Confirmed known hematopoiesis mechanisms and generated new hypotheses.

Conclusions:

The network inference method accurately models HSC differentiation.
Gata2 plays a critical role in directing HSC lineage commitment.
This approach is broadly applicable to uncovering regulatory relationships in hierarchical biological systems.