Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

Abstract

Hematopoietic stem cells (HSCs) generated during embryonic development are able to maintain hematopoiesis for the lifetime, producing all mature blood lineages. HSC transplantation is a widely used cell therapy intervention in the treatment of hematologic, autoimmune and genetic disorders. Its use, however, is hampered by the inability to expand HSCs ex vivo, urging for a better understanding of the mechanisms regulating their physiological expansion. In the adult, HSCs reside in the bone marrow, in specific microenvironments that support stem cell maintenance and differentiation. Conversely, while developing, HSCs are transiently present in the fetal liver, the major hematopoietic site in the embryo, where they expand. Deeper insights on the dynamics of fetal liver composition along development, and on how these different cell types impact hematopoiesis, are needed. Both, the hematopoietic and hepatic fetal systems have been extensively studied, albeit independently. This review aims to explore their concurrent establishment and evaluate to what degree they may cross modulate their respective development. As insights on the molecular networks that govern physiological HSC expansion accumulate, it is foreseeable that strategies to enhance HSC proliferation will be improved.

Macrophages Derived From Human Induced Pluripotent Stem Cells: The Diversity of Protocols, Future Prospects, and Outstanding Questions

“…Accordingly, TPO supports megakaryocyte differentiation and maintains HSC survival; it also has promyelocytic effect. In steady-state conditions, TPO supports HSC quiescence ( Alexander et al, 1996 ; Ballmaier et al, 2003 ; Yoshihara et al, 2007 ; de Graaf and Metcalf, 2011 ; Decker et al, 2018 ); in posttransplantation conditions, it induces HSC self-renewal and expansion ( Fox et al, 2002 ; Soares-da-Silva et al, 2020 ). During embryogenesis, TPO was shown to support the survival and the expansion of HSCs in mouse fetal liver ( Petit-Cocault et al, 2007 ); its role in YS hematopoiesis is less clear.…”

“…In vitro , TPO supports megakaryocyte progenitors and promotes the survival and the proliferation of BM HSPCs; the effects are enhanced in the presence of Flt3L and SCF ( Ramsfjell et al, 1996 ; Borge et al, 1997 ; Zhang et al, 2018 ). Forced expression of TPO in human ESCs had promegakaryocytic and promyeloid effects ( de Graaf and Metcalf, 2011 ; Soares-da-Silva et al, 2020 ).…”

Neonatal hepatic myeloid progenitors expand and propagate liver inflammation in mice

“…Our findings also support the idea that liver inflammation during perinatal life affects emigrating hepatic progenitor populations. In humans, the spatial and temporal overlap of liver development and hematopoiesis in the late-gestational fetus[17] may contribute to the devastating acute and chronic consequences of both liver- and immune function observed in progressive inflammatory diseases like BA. In our study, perinatal liver injury led to an early increase in HSPCs and depletion of these cells lessened clinical and histological signs of liver inflammation.…”

Liver Regeneration by Hematopoietic Stem Cells: Have We Reached the End of the Road?

“…The three overlapping waves of embryonic hematopoiesis consisting of hematopoietic progenitors and definitive HSCs home and colonise the fetal liver at E11.5 in mouse and around 6 weeks post conception in humans. HSCs and other progenitors are also found in the fetal spleen after E15.5 and in the bone marrow at E17.5 [ 64 , 65 ].…”