Fetal/Embryonic Hematopoietic Progenitors and Their Impact on Adult Diseases

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About this Research Topic

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Background

The embryonic origin of the hematopoietic system has been extensively studied; however, a complete picture of hematopoietic development is still missing. The orthodox paradigm divided hematopoiesis as primitive versus definitive. in which the former generated mainly nucleated primitive erythrocytes (EryP) and definitive hematopoiesis contained all hematopoietic lineages, including nucleated and enucleated definitive erythrocytes (EryD) and hematopoietic stem cells (HSCs) with long-term repopulating activity. Another dogma originating from studies of hematopoiesis in the adult organism is that HSCs reside at the top of the hematopoietic hierarchy.

Recent advances including the use of new in vitro and in vivo model systems enabling conditional knockout approaches, sophisticated genetic lineage tracing strategies, and genome-wide analyses at single cell level has allowed the gathering of more and more evidences challenging this binary view. It is now clear that HSC function is largely dispensable during early development, and HSC appearance is preceded by the emergence of other hematopoietic progenitor cells (HSC-independent hematopoiesis). For instance, the yolk sac has been demonstrated to be one of the sources of non HSC progenitors with multipotent potential, e.g. erythro-myeloid progenitors (EMPs) and lympho-myeloid progenitors (LMPPs). EMPs were previously considered transient, but they have recently been shown to be the main source of adult tissue resident macrophages which persist and self-renew independently from HSCs. Also, some innate lymphocytes are formed mainly during fetal and postnatal life and are sustained in adulthood by self-renewal. As fetal hematopoiesis is more relevant than previously thought, this implies that EMPs and other embryonic and fetal progenitors could be subject to genetic lesions leading to diseases later in development and in adults. It is therefore important to gain insight into the intrinsic and extrinsic (micro-environmental) cues playing a role in the molecular regulation of embryonic and fetal hematopoiesis, and understand how and to what extent they differ from adult hematopoiesis.

This Research Topic aims to showcase the recent progress in the study of the molecular factors involved in all steps of embryonic and fetal hematopoiesis, from development to function. We welcome the submission of Original Research, Methods, Review and Mini-Review articles that cover, but are not limited to, the following topics:

• Revised ontogeny
• Contribution of fetal cells to disease and potential implications
• New cellular and molecular tools
• Therapeutic implications

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Keywords: Hematopoiesis, Hematopoietic Stem Cells, Progenitors, Embryo, Disease

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