Hepatoblasts comprise a niche for fetal liver erythropoiesis through cytokine production

Sugiyama, Daisuke; Kulkeaw, Kasem; Mizuochi, Chiyo; Horio, Yuka; Okayama, Satoko

doi:10.1016/j.bbrc.2011.05.137

Cited by 44 publications

(35 citation statements)

References 26 publications

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“…The morphology and phenotype of liver epithelial cells change in the course of development, and these changes correlate with hematopoietic activity [4,5]. Cells of the hepatocyte lineage appear to play an important role in the regulation of erythropoiesis: they closely interact with erythroblasts [5] and produce erythropoietic cytokines such as stem cell factor and erythropoietin [6,7].…”

Section: Liver Epitheliummentioning

confidence: 99%

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

Payushina

2012

ISRN Cell Biology

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Hematopoiesis is the main function of the liver during a considerable period of mammalian prenatal development. Hematopoietic cells of the fetal liver exist in a specific microenvironment that controls their proliferation and differentiation. This microenvironment is created by different cell populations, including epitheliocytes, macrophages, various stromal elements (hepatic stellate cells, fibroblasts, myofibroblasts, vascular smooth muscle and endothelial cells, mesenchymal stromal cells), and also cells undergoing epithelial-to-mesenchymal transition. This paper considers the involvement of these cell types in the regulation of fetal liver hematopoiesis.

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Section: Liver Epitheliummentioning

confidence: 99%

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

Payushina

2012

ISRN Cell Biology

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“…HSPCs generated in the yolk sac, AGM region and placenta are thought to migrate and home to FL from E9.5 [373839404142]. Hematopoietic activity in FL begins shortly after liver development commences at E10.5 and is active at E11.5.…”

Section: Introductionmentioning

confidence: 99%

“…Hepatoblasts differentiate into hepatic cells and biliary epithelial cells and express Delta-like 1 homolog (DLK1) [39]. DLK1 + hepatoblasts can be found adjacent to the HSPCs expressing the stem cell factor receptor c-Kit (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Since the erythroblastic island is found in close proximity to hepatoblasts, this niche structure and expression pattern of hematopoietic factors is highly supportive of erythropoiesis. Evidence supporting a role of hepatoblasts comes from Map2k4 -deficient mice which lack hepatoblasts [39]. In Map2k4 -deficient animals, the frequency of hematopoietic cell is reduced to half of the number observed in wild type mouse embryos.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of the embryonic erythropoietic niche: a future perspective

2017

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The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1+ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1+ hepatoblasts in Map2k4−/− mouse embryos resulted in decreased numbers of hematopoietic cells in fetal liver. Genes encoding proteinases and peptidases were found to be highly expressed in DLK1+ hepatoblasts. Capitalizing on this knowledge, and working on the assumption that these proteinases and peptidases are generating small, potentially biologically active peptides, we assessed a range of peptides for their ability to support erythropoiesis in vitro. We identified KS-13 (PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the production of red blood cells from progenitor cells. Here, we discuss the elements regulating embryonic erythropoiesis with special attention to niche cells, and demonstrate how this knowledge can be applied in the identification of niche-derived peptides with potential therapeutic capability.

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“…The FL haematopoietic niche consists of a variety of cell types including maturing haematopoietic cells themselves, sinusoidal endothelial cells, macrophages, stromal fibroblasts, and hepatoblasts (progenitors of hepatocytes). Hepatoblasts produce a broad range of haematopoietic growth factors including SCF, erythropoietin (Epo), thrombopoietin (TPO), and IL-6 which all support erythroid cell development [56]. The role of hepatoblasts in supporting haematopoiesis is best exemplified by mice lacking the tyrosine kinase Map2k4.…”

Section: Embryonic Haematopoietic Nichesmentioning

confidence: 99%

Making Blood: The Haematopoietic Niche throughout Ontogeny

Al-Drees

Yeo

Boumelhem

et al. 2015

Stem Cells International

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Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells. Supporting cells serve to maintain haematopoietic stem and progenitor cells during homeostatic and pathological conditions. This coalition of supportive cell types, organised in specific tissues, is termed the haematopoietic niche. Haematopoietic stem and progenitor cells are generated in a number of distinct locations during mammalian embryogenesis. These stem and progenitor cells migrate to a variety of anatomical locations through the conceptus until finally homing to the bone marrow shortly before birth. Under stress, extramedullary haematopoiesis can take place in regions that are typically lacking in blood-producing activity. Our aim in this review is to examine blood production throughout the embryo and adult, under normal and pathological conditions, to identify commonalities and distinctions between each niche. A clearer understanding of the mechanism underlying each haematopoietic niche can be applied to improving ex vivo cultures of haematopoietic stem cells and potentially lead to new directions for transplantation medicine.

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Hepatoblasts comprise a niche for fetal liver erythropoiesis through cytokine production

Cited by 44 publications

References 26 publications

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

Hematopoietic Microenvironment in the Fetal Liver: Roles of Different Cell Populations

Regulation of the embryonic erythropoietic niche: a future perspective

Making Blood: The Haematopoietic Niche throughout Ontogeny

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