Abstract
SummaryThe differentiation of human embryonic stem cells (hESCs) to hematopoietic lineages initiates with the specification of hemogenic endothelium, a transient specialized endothelial precursor of all blood cells. This in vitro system provides an invaluable model to dissect the emergence of hematopoiesis in humans. However, the study of hematopoiesis specification is hampered by a lack of consensus in the timing of hemogenic endothelium analysis and the full hematopoietic potential of this population. Here, our data reveal a sharp decline in the hemogenic potential of endothelium populations isolated over the course of hESC differentiation. Furthermore, by tracking the dynamic expression of CD31 and CD235a at the onset of hematopoiesis, we identified three populations of hematopoietic progenitors, representing primitive and definitive subsets that all emerge from the earliest specified hemogenic endothelium. Our data establish that hemogenic endothelium populations endowed with primitive and definitive hematopoietic potential are specified simultaneously from the mesoderm in differentiating hESCs.
Highlights
The hemogenic endothelium (HE) has been described as an intermediate endothelial precursor of all hematopoietic progenitors in the human embryo (Ivanovs et al, 2017; Julien et al, 2016)
Transcriptional Landscape of Endothelium Precursor Populations during the Course of embryoid body (EB) Differentiation To address how timing of human embryonic stem cells (hESCs) differentiation might affect hemogenic potential, we first analyzed the emergence of endothelium cell populations during EB differentiation
Similar to studies performed on OP9 co-culture (Choi et al, 2012; Rafii et al, 2013), a significant CD31+CD144+ endothelial population was detected by day 5 of EB differentiation (Figure S1A)
Summary
The hemogenic endothelium (HE) has been described as an intermediate endothelial precursor of all hematopoietic progenitors in the human embryo (Ivanovs et al, 2017; Julien et al, 2016). The efficiency of hematopoietic differentiation differs between the two methodologies due to parameters such as serum, stromal maintenance, or EB size, among others factors (Kardel and Eaves, 2012; Vodyanik et al, 2006). In both of these experimental approaches, the hemogenic potential of endothelium precursor population has been analyzed at different times of the differentiation process, with or without a prior purification step of this population (Ditadi et al, 2015; Ramos-Mejia et al, 2014). Together these variations in experimental approaches make it difficult to reach clear conclusions and consensus about the nature and potential of HE cells
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