Hepatic stellate and endothelial cells maintain hematopoietic stem cells in the developing liver

Lee, Yeojin; Leslie, Juliana; Yang, Ying; Ding, Lei

doi:10.1084/jem.20200882

Cited by 32 publications

(36 citation statements)

References 49 publications

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“…Cxcl12 and Kit ligand mediate HSPCs homing into the fetal liver 134 and both of these factors are produced by hepatic stellate cells, 135‐137 in addition to a collection of cytokines that regulate the immune cells fate 138 …”

Section: Stromal and Immune Interactions Beyond Scarringmentioning

confidence: 99%

“…Cxcl12 and Kit ligand mediate HSPCs homing into the fetal liver 134 and both of these factors are produced by hepatic stellate cells, [135][136][137] in addition to a collection of cytokines that regulate the immune cells fate. 138 Hepatic stellate cells secrete insulin-like growth factor II (Igf2) which binds to its receptor Igf2r on HSPCs promoting their proliferation 136,139 while Igf2 reduction hampers fetal liver hematopoiesis.…”

Section: Mesothelial-derived Stromal Cells Regulate Hematopoiesis In the Fetal Livermentioning

confidence: 99%

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Fibroblasts as confederates of the immune system

Correa-Gallegos

Jiang

Rinkevich

2021

Immunological Reviews

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| 147 wileyonlinelibrary.com/journal/imr 1 | INTRODUC TI ON "Stromal" cell refers to the cellular component that form and maintain the structural parts of an organ, whereas parenchymal cells perform the specific organ function. Stromal cells, such as fibroblasts, have traditionally been considered as quiescent cells that primarily function to make extracellular matrices. Relevant in the clinic, these cells contribute to excessive connective tissue formation during injury repair, cancer, and fibrosis. However, these dedicated cells, and the niches they create, also orchestrate immunological functions by influencing the differentiation, movement, and activation of immune cells. Recent genetic lineage-tracing and single-cell RNA sequencing studies highlight the diversity of stromal cell populations in tissues and revealed how eclectic stromal cells orchestrate the diversity of immunological functions.These days, fibroblasts are no longer considered as mere structural components of organs but as dynamic participants in immune processes. We discuss four major mechanisms by which fibroblasts and immune cells interact: (a) paracrine signaling via cytokine and chemokine secretion, (b) direct priming via juxtacrine interactions, and (c) behavioral modulation through extracellular matrix remodeling. Finally, and more recently described, (d) transfer or mobilization of extracellular matrix microenvironments. In the following sections, we review the impact of these four modes of interaction between distinct fibroblast populations and immune cells during homeostasis, injury repair, scarring, and disease in the mammalian skin. Finally, we discuss the origins, of these and other stromal lineages, and their

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Section: Stromal and Immune Interactions Beyond Scarringmentioning

confidence: 99%

Section: Mesothelial-derived Stromal Cells Regulate Hematopoiesis In the Fetal Livermentioning

confidence: 99%

Fibroblasts as confederates of the immune system

Correa-Gallegos

Jiang

Rinkevich

2021

Immunological Reviews

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“…The reduction in liver HSCs could be due to enhanced egress, as HSCs actively seed the spleen and bone marrow at the perinatal stage. To address this, we also analyzed mice at P5, when HSCs are in migration from the liver to the bone marrow ( 17 ). HSC frequency was significantly reduced to a similar extent in P5 Tpo −/− livers, bone marrow, and spleens (fig.…”

Section: Resultsmentioning

confidence: 99%

Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver

et al. 2022

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Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of Tpo reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in Tpo −/− mice. Enforced activation of the mTOR pathway by conditionally deleting Tsc1 significantly rescued HSCs and their gene expression in Tpo −/− mice. Lin28b intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of Lin28b further reduced mTOR activity and strongly exacerbated HSC depletion in Tpo −/− mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver.

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“…A mouse single-cell molecular map during gastrulation and mesoderm diversification validated the origin of the hematoendothelial lineages with the expression of Flk1/ Kdr and Tal1 as molecular switch determining lineage fate to either EC or hematopoietic cells during mesoderm diversification [43,44]. Hematopoietic cells then further develop and are maintained by the niches within the developing liver, typically by EC and HSC through paracrine-acting stem cell factor [45]. Temporally restricted lineage-tracing experiment of Cdh5-expressing cells demonstrated the contribution of common progenitor cells to the liver vasculature [46].…”

Section: Development Of Liver Sinusoidal Endothelial Cells and Their mentioning

confidence: 88%

Angiodiversity and organotypic functions of sinusoidal endothelial cells

et al. 2021

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Abstract‘Angiodiversity’ refers to the structural and functional heterogeneity of endothelial cells (EC) along the segments of the vascular tree and especially within the microvascular beds of different organs. Organotypically differentiated EC ranging from continuous, barrier-forming endothelium to discontinuous, fenestrated endothelium perform organ-specific functions such as the maintenance of the tightly sealed blood–brain barrier or the clearance of macromolecular waste products from the peripheral blood by liver EC-expressed scavenger receptors. The microvascular bed of the liver, composed of discontinuous, fenestrated liver sinusoidal endothelial cells (LSEC), is a prime example of organ-specific angiodiversity. Anatomy and development of LSEC have been extensively studied by electron microscopy as well as linage-tracing experiments. Recent advances in cell isolation and bulk transcriptomics or single-cell RNA sequencing techniques allowed the identification of distinct LSEC molecular programs and have led to the identification of LSEC subpopulations. LSEC execute homeostatic functions such as fine tuning the vascular tone, clearing noxious substances from the circulation, and modulating immunoregulatory mechanisms. In recent years, the identification and functional analysis of LSEC-derived angiocrine signals, which control liver homeostasis and disease pathogenesis in an instructive manner, marks a major change of paradigm in the understanding of liver function in health and disease. This review summarizes recent advances in the understanding of liver vascular angiodiversity and the functional consequences resulting thereof.

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Hepatic stellate and endothelial cells maintain hematopoietic stem cells in the developing liver

Cited by 32 publications

References 49 publications

Fibroblasts as confederates of the immune system

Fibroblasts as confederates of the immune system

Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver

Angiodiversity and organotypic functions of sinusoidal endothelial cells

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