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 ++ CD45 low ) 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 hematopoietic in vivo engraftment 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.

Human haematopoietic stem cell development: from the embryo to the dish

“…Although CD34 + cells appear in the human placenta as early as at week 5 of gestation, true HSCs can be detected there only after week 9 of gestation or even later, as determined by xenotransplantation into immunocompromised mice (Robin et al, 2009;Muench et al, 2017). Although the CD34 ++ CD45 lo population that contains HSCs is embedded within a vimentin-positive stromal environment or rarely in close association with blood vessels (Muench et al, 2017), localisation of the exact HSC fraction and their regulatory microenvironment in the human placenta is currently unavailable.…”

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

“…HSCs are generated in the dorsal aorta of the aorta-gonad-mesonephros (AGM) region, subsequently migrate to the fetal liver, and lodge in the adult bone marrow ( Ivanovs et al, 2011 , 2017 ; Tavian et al, 2010 ). In addition, the placenta was identified as a site for human HSC development ( Muench et al, 2017 ; Robin et al, 2009 ). Human HSCs develop from an intermediate hemogenic precursor cell with endothelial properties between days 27 and 40 ( Ivanovs et al, 2017 ; Oberlin et al, 2002 ).…”

Hierarchical organization of developing HSPC in the human embryonic liver

“…In contrast to the YS and AGM, the 5 to 9.6 week placentas show only few DP cells. Despite the fact that CD34 + cells are detected as early as week 5 of gestation in the human placenta (Barcena et al, 2009), repopulating HSPCs are present at week 6 of gestation (Robin et al, 2009) although two studies report the presence of transplantable HSPCs only after week 9 of gestation or even later, as determined by xenotransplantation into immunocompromised mice Muench et al, 2017). These latest observations and the fact that we could only identify few DP cells in the 5-9.6…”