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Updated: Jun 15, 2026

Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
Published on: November 1, 2017
Developmental niches for embryonic erythroid cells
Joan Isern1, Stuart T Fraser, Zhiyong He
1Department of Medicine (Division of Hematology and Medical Oncology), Mount Sinai School of Medicine, New York, NY 10029, USA.
Insights
Researchers tracked primitive erythroid cells (EryP) during mammalian embryogenesis using a novel fluorescent reporter mouse. This method allowed detailed monitoring of EryP development across multiple embryonic tissues.
Area of Science:
- Developmental Biology
- Hematopoiesis
- Genetics
Background:
- Primitive erythroid cells (EryP) are the initial differentiated cell type in mammalian embryogenesis.
- EryP originate in the yolk sac (YS) and mature within the embryonic circulation.
- Tracking EryP maturation is challenging due to their decreasing numbers relative to definitive erythroid cells (EryD) later in development.
Purpose of the Study:
- To develop a method for tracking and quantifying primitive erythroid cells (EryP) during mammalian embryogenesis.
- To monitor EryP development and differentiation across distinct embryonic niches.
Main Methods:
- Utilized a transgenic fluorescent reporter mouse line.
- Employed human epsilon-globin gene regulatory elements to drive lineage-specific histone-H2B::EGFP expression.
- Labeled EryP chromatin for tracking and quantification of nuclei post-expulsion.
Main Results:
- Successfully monitored primitive erythropoiesis in the yolk sac, embryonic circulation, and fetal liver.
- Enabled tracking of EryP development from progenitor stage to terminal differentiation.
- Quantified EryP nuclei following their expulsion from maturing cells.
Conclusions:
- The developed transgenic reporter system is effective for studying primitive erythropoiesis.
- This method provides new insights into the maturational stages of EryP in vivo.
- Facilitates detailed analysis of EryP development across key embryonic hematopoietic sites.
Abstract:
Primitive erythroid cells (EryP) are the first differentiated cell type to be specified during mammalian embryogenesis. EryP arise from a pool of lineage-restricted progenitors in the yolk sac (YS) and then enter the newly formed embryonic circulation to mature in a stepwise, synchronous fashion. Numbering in the millions in the mid-gestation mouse embryo, EryP are the dominant circulating blood cell prior to the rapid generation of adult-type definitive erythroid (EryD) cells in the fetal liver. The identification of maturational events in this lineage presented a significant challenge, as EryD begin to outnumber EryP in the bloodstream from approximately E14.5 onwards. We used human epsilon-globin gene regulatory elements to drive lineage-specific expression of a histone-H2B::EGFP fusion protein, allowing us to label the chromatin of EryP during their development and to track and quantify EryP nuclei following their expulsion from the cell. Using this transgenic fluorescent reporter mouse line, we have monitored primitive erythropoiesis in three distinct niches: the YS, where EryP progenitors arise; the circulation, where EryP continue to divide and mature; and the fetal liver, where EryP complete the terminal stages of their differentiation.
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