Finding ways to produce hematopoietic stem cells (HSCs) in vitro is a prominent area of study because of their critical role in clinical practice. By limiting the size of the sympathetic nervous system (SNS) and the quantity of catecholamines released by these cells, researchers demonstrated in the study that the cell cycle inhibitor p57Kip2/Cdkn1c restricts the number of developing HSCs.

The control takes place at the level of the SNS progenitor and contrasts with p57Kip2’s intrinsic role in sustaining adult HSCs, underscoring the significant disparities between the adult and embryonic HSCs’ cell cycle needs. Furthermore, because early fetal liver HSC counts were also decreased, the effect was restricted to the aorta-gonad-mesonephros (AGM) area and demonstrated that the AGM is the primary contributor to early fetal liver colonization.

They demonstrated in vivo that intact β2-adrenergic signaling is necessary for SNS-dependent HSC growth by using a variety of antagonists. They created a single-cell RNA-sequencing data collection of all Ngfr+ sympathoadrenal cells around the dorsal aorta to analyze their differentiation route in order to acquire more molecular understanding. Importantly, it revealed that some neural crest cells are capable of taking an alternative differentiation pathway upon arrival at the aorta, giving rise to a subset of ventrally restricted mesenchymal cells that express significant HSC-supportive factors.

It not only defined the relevant p57Kip2-expressing SNS progenitor stage. Thus, it appeared that neural crest cells contribute to the AGM HSC niche by two distinct mechanisms: SNS-mediated catecholamine secretion and the generation of mesenchymal cells that support HSCs.

Reference: ashpublications.org/blood/article/140/5/464/485456/p57Kip2-regulates-embryonic-blood-stem-cells-by