Erythroid/Myeloid Progenitors and Hematopoietic Stem Cells Originate from Distinct Populations of Endothelial Cells

Chen, Michael; Li, Yan; Obaldia, Maria Elena De; Yang, Qi; Yzaguirre, Amanda D.; Yamada-Inagawa, Tomoko; Vink, Chris S.; Bhandoola, Avinash; Dzierzak, Elaine; Speck, Nancy A.

doi:10.1016/j.stem.2011.10.003

Cited by 228 publications

(204 citation statements)

References 55 publications

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“…8, top). This EMP population arises in the E8.25 yolk sac then seeds the fetal liver by E11.5, providing the first source of definitive erythroid progenitors prior to or coincident with colonization by distinct hematopoietic stem cell (HSC) sources (Chen et al, 2011;Lux et al, 2008;McGrath et al, 2011;Tober et al, 2013).…”

Section: Discussion Cellular and Mechanistic Aspects Of Erythroid/macmentioning

confidence: 99%

“…Another arises later (beginning at E8.25) and yields definitive erythroid as well as a varied set of myeloid progeny from a cell termed the erythro-myeloid progenitor (EMP). These transient waves precede the emergence of long-term hematopoietic stem cells during mammalian development from other sites of the embryo (Baron, 2013;Chen et al, 2011;Dzierzak and Speck, 2008;McGrath and Palis, 2005). Our observations on the clonal emergence of erythroid-macrophage islands that arise during primitive or definitive hematopoietic stages of ESC differentiation, the co-expression of EKLF in erythroid and an F4/80 subset of macrophage cells during definitive hematopoiesis, and the availability of the marked GFP mice prompted us to determine the specific cell-surface phenotype of EKLF/GFP+ cells.…”

Section: Eklf Onset During Erythroid-myeloid Generation In Early Devementioning

confidence: 99%

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Extrinsic and intrinsic control by EKLF (KLF1) within a specialized erythroid niche

et al. 2014

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The erythroblastic island provides an important nutritional and survival support niche for efficient erythropoietic differentiation. Island integrity is reliant on adhesive interactions between erythroid and macrophage cells. We show that erythroblastic islands can be formed from single progenitor cells present in differentiating embryoid bodies, and that these correspond to erythro-myeloid progenitors (EMPs) that first appear in the yolk sac of the early developing embryo. Erythroid Krüppel-like factor (EKLF; KLF1), a crucial zinc finger transcription factor, is expressed in the EMPs, and plays an extrinsic role in erythroid maturation by being expressed in the supportive macrophage of the erythroblastic island and regulating relevant genes important for island integrity within these cells. Together with its well-established intrinsic contributions to erythropoiesis, EKLF thus plays a coordinating role between two different cell types whose interaction provides the optimal environment to generate a mature red blood cell.

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Section: Discussion Cellular and Mechanistic Aspects Of Erythroid/macmentioning

confidence: 99%

Section: Eklf Onset During Erythroid-myeloid Generation In Early Devementioning

confidence: 99%

Extrinsic and intrinsic control by EKLF (KLF1) within a specialized erythroid niche

et al. 2014

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“…1 D). Interestingly, most cells that were positive for Sca1-GFP, which marks the emerging HSCs in the endothelium Chen et al, 2011), also coexpressed phospho-CREB (Fig. 1 E).…”

Section: Creb Activation In the Agmmentioning

confidence: 96%

Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence

Kim¹,

Nakano²,

Das³

et al. 2015

J Cell Biol

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Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aortagonad-mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP response elementbinding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA-CREB and BMP pathways in isolated AGM VEcadherin + cells from mid-gestation embryos, we demonstrate that PKA-CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA-CREB-BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-tohematopoietic transition.

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“…Hemogenic endothelial cells are integral to the aortic wall (Bertrand et al, 2010;Chen et al, 2011;de Bruijn et al, 2002;Jaffredo et al, 1998;North et al, 1999) and undergo a characteristic morphological change during EHT (Kissa and Herbomel, 2010). To determine whether gata2b + cells in gata2b: Gal4 animals behave in a similar way, we analyzed gata2b:Gal4 in the context of the pan-vascular marker kdrl.…”

Section: Gata2b Is Expressed In Hematopoietic Precursor Cellsmentioning

confidence: 99%

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

et al. 2015

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The adult blood system is established by hematopoietic stem cells (HSCs), which arise during development from an endothelial-tohematopoietic transition of cells comprising the floor of the dorsal aorta. Expression of aortic runx1 has served as an early marker of HSC commitment in the zebrafish embryo, but recent studies have suggested that HSC specification begins during the convergence of posterior lateral plate mesoderm (PLM), well before aorta formation and runx1 transcription. Further understanding of the earliest stages of HSC specification necessitates an earlier marker of hemogenic endothelium. Studies in mice have suggested that GATA2 might function at early stages within hemogenic endothelium. Two orthologs of Gata2 exist in zebrafish: gata2a and gata2b. Here, we report that gata2b expression initiates during the convergence of PLM, becoming restricted to emerging HSCs. We observe Notch-dependent gata2b expression within the hemogenic subcompartment of the dorsal aorta that is in turn required to initiate runx1 expression. Our results indicate that Gata2b functions within hemogenic endothelium from an early stage, whereas Gata2a functions more broadly throughout the vascular system.

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Erythroid/Myeloid Progenitors and Hematopoietic Stem Cells Originate from Distinct Populations of Endothelial Cells

Cited by 228 publications

References 55 publications

Extrinsic and intrinsic control by EKLF (KLF1) within a specialized erythroid niche

Extrinsic and intrinsic control by EKLF (KLF1) within a specialized erythroid niche

Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence

Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo

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