title: The human chorion contains definitive hematopoietic stem cells from the fifteenth week of gestation.
abstract: We examined the contribution of the fetal membranes, amnion and chorion, to human embryonic and fetal hematopoiesis. A population of cells displaying a hematopoietic progenitor phenotype (CD34++CD45low) of fetal origin was present in the chorion at all gestational ages, associated with stromal cells or near blood vessels, but was absent in the amnion. Prior to 15 weeks of gestation, these cells lacked hematopoieticin vivoengraftment potential. Differences in the chemokine receptor and β1 integrin expression profiles of progenitors between the first and second trimesters suggest that these cells had gestationally regulated responses to homing signals and/or adhesion mechanisms that influenced their ability to colonize the stem cell niche. Definitive hematopoietic stem cells, capable of multilineage and long-term reconstitution when transplanted in immunodeficient mice, were present in the chorion from 15-24 weeks gestation, but were absent at term. The second trimester cells also engrafted secondary recipients in serial transplantation experiments. Thus, the human chorion contains functionally mature hematopoietic stem cells at mid-gestation.
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA.|Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: Marcus O
authors.identifier: 0000-0001-8946-6605
authors.initials: MO
authors.lastname: Muench
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Mirhan
authors.initials: M
authors.lastname: Kapidzic
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Matthew
authors.identifier: 0000-0003-2042-1534
authors.initials: M
authors.lastname: Gormley
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Alan G
authors.identifier: 0000-0002-8567-9598
authors.initials: AG
authors.lastname: Gutierrez
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Ponder
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA.
authors.forename: Marina E
authors.identifier: 0000-0002-1573-8126
authors.initials: ME
authors.lastname: Fomin
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA.
authors.forename: Ashley I
authors.identifier: 0000-0002-9306-3515
authors.initials: AI
authors.lastname: Beyer
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Haley
authors.identifier: 0000-0003-1635-894X
authors.initials: H
authors.lastname: Stolp
authors.affiliation: Department of Laboratory Medicine, Clinical Cytogenetics Laboratory, University of California, San Francisco, CA 94107, USA.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Qi
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
authors.affiliation: The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA Alicia.Barcena@ucsf.edu.|Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Alicia
authors.identifier: 0000-0003-3463-0628
authors.initials: A
authors.lastname: Bárcena
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D019070:Cell Lineage; D002823:Chorion / Q000166:cytology* / Q000637:transplantation; D002824:Chorionic Villi / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016513:Mice, SCID; D010641:Phenotype; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D019707:Receptors, Chemokine; D014357:Trypsin; D017364:Collagenases
keywords: Chorion; Extraembryonic development; Hematopoietic development; Human hematopoietic stem cells