Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression
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Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression. / Anderson, Heidi; Patch, Taylor C; Reddy, Pavankumar N G; Hagedorn, Elliott J; Kim, Peter G; Soltis, Kathleen A; Chen, Michael J; Tamplin, Owen J; Frye, Maike; MacLean, Glenn A; Hübner, Kathleen; Bauer, Daniel E; Kanki, John P; Vogin, Guillaume; Huston, Nicholas C; Nguyen, Minh; Fujiwara, Yuko; Paw, Barry H; Vestweber, Dietmar; Zon, Leonard I; Orkin, Stuart H; Daley, George Q; Shah, Dhvanit I.
In: BLOOD, Vol. 126, No. 26, 24.12.2015, p. 2811-20.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression
AU - Anderson, Heidi
AU - Patch, Taylor C
AU - Reddy, Pavankumar N G
AU - Hagedorn, Elliott J
AU - Kim, Peter G
AU - Soltis, Kathleen A
AU - Chen, Michael J
AU - Tamplin, Owen J
AU - Frye, Maike
AU - MacLean, Glenn A
AU - Hübner, Kathleen
AU - Bauer, Daniel E
AU - Kanki, John P
AU - Vogin, Guillaume
AU - Huston, Nicholas C
AU - Nguyen, Minh
AU - Fujiwara, Yuko
AU - Paw, Barry H
AU - Vestweber, Dietmar
AU - Zon, Leonard I
AU - Orkin, Stuart H
AU - Daley, George Q
AU - Shah, Dhvanit I
N1 - © 2015 by The American Society of Hematology.
PY - 2015/12/24
Y1 - 2015/12/24
N2 - Rare endothelial cells in the aorta-gonad-mesonephros (AGM) transition into hematopoietic stem cells (HSCs) during embryonic development. Lineage tracing experiments indicate that HSCs emerge from cadherin 5 (Cdh5; vascular endothelial-cadherin)(+) endothelial precursors, and isolated populations of Cdh5(+) cells from mouse embryos and embryonic stem cells can be differentiated into hematopoietic cells. Cdh5 has also been widely implicated as a marker of AGM-derived hemogenic endothelial cells. Because Cdh5(-/-) mice embryos die before the first HSCs emerge, it is unknown whether Cdh5 has a direct role in HSC emergence. Our previous genetic screen yielded malbec (mlb(bw306)), a zebrafish mutant for cdh5, with normal embryonic and definitive blood. Using time-lapse confocal imaging, parabiotic surgical pairing of zebrafish embryos, and blastula transplantation assays, we show that HSCs emerge, migrate, engraft, and differentiate in the absence of cdh5 expression. By tracing Cdh5(-/-)green fluorescent protein (GFP)(+/+) cells in chimeric mice, we demonstrated that Cdh5(-/-)GFP(+/+) HSCs emerging from embryonic day 10.5 and 11.5 (E10.5 and E11.5) AGM or derived from E13.5 fetal liver not only differentiate into hematopoietic colonies but also engraft and reconstitute multilineage adult blood. We also developed a conditional mouse Cdh5 knockout (Cdh5(flox/flox):Scl-Cre-ER(T)) and demonstrated that multipotent hematopoietic colonies form despite the absence of Cdh5. These data establish that Cdh5, a marker of hemogenic endothelium in the AGM, is dispensable for the transition of hemogenic endothelium to HSCs.
AB - Rare endothelial cells in the aorta-gonad-mesonephros (AGM) transition into hematopoietic stem cells (HSCs) during embryonic development. Lineage tracing experiments indicate that HSCs emerge from cadherin 5 (Cdh5; vascular endothelial-cadherin)(+) endothelial precursors, and isolated populations of Cdh5(+) cells from mouse embryos and embryonic stem cells can be differentiated into hematopoietic cells. Cdh5 has also been widely implicated as a marker of AGM-derived hemogenic endothelial cells. Because Cdh5(-/-) mice embryos die before the first HSCs emerge, it is unknown whether Cdh5 has a direct role in HSC emergence. Our previous genetic screen yielded malbec (mlb(bw306)), a zebrafish mutant for cdh5, with normal embryonic and definitive blood. Using time-lapse confocal imaging, parabiotic surgical pairing of zebrafish embryos, and blastula transplantation assays, we show that HSCs emerge, migrate, engraft, and differentiate in the absence of cdh5 expression. By tracing Cdh5(-/-)green fluorescent protein (GFP)(+/+) cells in chimeric mice, we demonstrated that Cdh5(-/-)GFP(+/+) HSCs emerging from embryonic day 10.5 and 11.5 (E10.5 and E11.5) AGM or derived from E13.5 fetal liver not only differentiate into hematopoietic colonies but also engraft and reconstitute multilineage adult blood. We also developed a conditional mouse Cdh5 knockout (Cdh5(flox/flox):Scl-Cre-ER(T)) and demonstrated that multipotent hematopoietic colonies form despite the absence of Cdh5. These data establish that Cdh5, a marker of hemogenic endothelium in the AGM, is dispensable for the transition of hemogenic endothelium to HSCs.
KW - Animals
KW - Antigens, CD
KW - Cadherins
KW - Cell Differentiation
KW - Cell Lineage
KW - Electroporation
KW - Embryo, Mammalian
KW - Embryo, Nonmammalian
KW - Flow Cytometry
KW - Hemangioblasts
KW - Hematopoiesis
KW - Hematopoietic Stem Cells
KW - Immunohistochemistry
KW - Mesonephros
KW - Mice
KW - Mice, Knockout
KW - Microscopy, Confocal
KW - Zebrafish
KW - Journal Article
U2 - 10.1182/blood-2015-07-659276
DO - 10.1182/blood-2015-07-659276
M3 - SCORING: Journal article
C2 - 26385351
VL - 126
SP - 2811
EP - 2820
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 26
ER -