Abstract
The journey of a hematopoietic stem cell (HSC) involves the passage through successive anatomical sites where HSCs are in direct contact with their surrounding microenvironment, also known as niche. These spatial and temporal cellular interactions throughout development are required for the acquisition of stem cell properties, and for maintaining the HSC pool through balancing self-renewal, quiescence and lineage commitment. Understanding the context and consequences of these interactions will be imperative for our understanding of HSC biology and will lead to the improvement of in vitro production of HSCs for clinical purposes. The aorta-gonad-mesonephros (AGM) region is in this light of particular interest since this is the cradle of HSC emergence during the embryonic development of all vertebrate species. In this review, we will focus on the developmental origin of HSCs and will discuss the novel technological approaches and recent progress made to identify the cellular composition of the HSC supportive niche and the underlying molecular events occurring in the AGM region.
Highlights
The origin of the hematopoietic system lies within the early developing embryo [1,2,3,4,5]
This study demonstrated that ‘niche’ cells are not necessarily in direct contact nor need to be in contact with hematopoietic stem cell (HSC) to fulfil their support capacity since secreted factors from the microenvironment are sufficient to maintain the HSC stemness properties [134]
An increasing number of studies based on RNA-sequencing and/or spatial transcriptomics performed in different embryo species confirmed the complexity of the aortic niche
Summary
The origin of the hematopoietic system lies within the early developing embryo [1,2,3,4,5]. The YS and the developing dorsal aorta in the para-aortic splanchnopleura (which will give rise to the AGM region) generate lymphoid progenitors at ∼E8.5 - E9.5, independently of HSCs, that are responsible for the initial immunity during development and the persistence of some immune cells (i.e. Bcells) into adulthood [29,30,31,32,33] The importance of these long thought short-life “primitive” hematopoietic cells, of which some subsist and play important roles in late fetuses and adults, reinforces the need for a better identification of the niche-derived signals regulating their production. The continued existence of HE cells beyond embryonic stages, leading to the formation of multipotent progenitors (MPP-3) and few HSCs in the sinusoids of the BM in fetal/neonate chicken and mouse was reported and imaged, which could be referred to as a 4th hematopoietic wave [70]
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