title: Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells.
abstract: Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1(+)Sca1(+)CD34(+)CD45(-) (PS34CD45(-)). Guided by these studies, we analyzed mouse placentas and identified a population with this phenotype. These cells express endothelial markers, are heterogeneous for early hematopoietic markers, and localize to the vascular labyrinth. Remarkably, global gene expression profiles of PS34CD45(-) cells correlate with reprogrammed precursors and establish a hemogenic precursor cell molecular signature. PS34CD45(-) cells are also present in intra-embryonic hemogenic sites. After stromal co-culture, PS34CD45(-) cells give rise to all blood lineages and engraft primary and secondary immunodeficient mice. In summary, we show that reprogramming reveals a phenotype for in vivo precursors to hemogenic endothelium, establishing that direct in vitro conversion informs developmental processes in vivo.
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, UC-Biotech, 3060-197 Cantanhede, Portugal. Electronic address: filipe.pereira@uc-biotech.pt.
authors.forename: Carlos-Filipe
authors.initials: CF
authors.lastname: Pereira
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Doctoral Programme in Experimental Biology and Biomedicine, University of Coimbra, 3004-517 Coimbra, Portugal; Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, UC-Biotech, 3060-197 Cantanhede, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Gomes
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bernitz
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papatsenko
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Niu
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Swiers
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Azzoni
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Marella F T R
authors.initials: MF
authors.lastname: de Bruijn
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaniel
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA.
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1496, New York, NY 10029, USA. Electronic address: kateri.moore@mssm.edu.
authors.forename: Kateri A
authors.initials: KA
authors.lastname: Moore
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004727:Endothelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D011247:Pregnancy