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Abstract
Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.
Keywords
BONE MORPHOGENETIC PROTEIN-4, MOUSE EMBRYO, DEFINITIVE HEMATOPOIESIS, DORSAL AORTA, FETAL LIVER, LEUKEMIA, EXPRESSION, PATHWAY, REGION, IDENTIFICATION

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Citation

Please use this url to cite or link to this publication:

Chicago
Crisan, Mihaela, Parham Solaimani Kartalaei, Alex Neagu, Sofia Karkanpouna, Tomoko Yamada-Inagawa, Caterina Purini, Chris S Vink, et al. 2016. “BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.” Stem Cell Reports 6 (3): 383–395.
APA
Crisan, M., Kartalaei, P. S., Neagu, A., Karkanpouna, S., Yamada-Inagawa, T., Purini, C., Vink, C. S., et al. (2016). BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo. STEM CELL REPORTS, 6(3), 383–395.
Vancouver
1.
Crisan M, Kartalaei PS, Neagu A, Karkanpouna S, Yamada-Inagawa T, Purini C, et al. BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo. STEM CELL REPORTS. 2016;6(3):383–95.
MLA
Crisan, Mihaela, Parham Solaimani Kartalaei, Alex Neagu, et al. “BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.” STEM CELL REPORTS 6.3 (2016): 383–395. Print.
@article{8500623,
  abstract     = {Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.},
  author       = {Crisan, Mihaela and Kartalaei, Parham Solaimani and Neagu, Alex and Karkanpouna, Sofia and Yamada-Inagawa, Tomoko and Purini, Caterina and Vink, Chris S and van der Linden, Reinier and van Ijcken, Wilfred and Chuva de Sousa Lopes, Susana Marina and Monteiro, Rui and Mummery, Christine and Dzierzak, Elaine},
  issn         = {2213-6711},
  journal      = {STEM CELL REPORTS},
  keyword      = {BONE MORPHOGENETIC PROTEIN-4,MOUSE EMBRYO,DEFINITIVE HEMATOPOIESIS,DORSAL AORTA,FETAL LIVER,LEUKEMIA,EXPRESSION,PATHWAY,REGION,IDENTIFICATION},
  language     = {eng},
  number       = {3},
  pages        = {383--395},
  title        = {BMP and Hedgehog regulate distinct AGM hematopoietic stem cells ex vivo},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2016.01.016},
  volume       = {6},
  year         = {2016},
}

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