Disruption of placental ACKR3 effects embryo, and offspring, growth and hematopoietic development.
Ayumi FukuokaGillian J WilsonElise PitmonLily Koumbas FoleyHanna JohnssonMarieke PingenGerard J GrahamPublished in: Development (Cambridge, England) (2024)
ACKR3 scavenges and degrades the stem cell recruiting chemokine CXCL12 which is essential for proper embryonic, and in particular hematopoietic development. Here we demonstrate strong expression of ACKR3 on trophoblasts. Using a maternally-administered pharmacological blocker, and Cre-mediated genetic approaches, we demonstrate that trophoblast ACKR3 is essential for preventing movement of CXCL12 from the mother to the embryo with elevated plasma CXCL12 levels being detected in embryos from ACKR3-blocker treated mothers. Mice born to mothers treated with the blocker are lighter and shorter than those born to vehicle-treated mothers and, in addition, display profound anaemia associated with a markedly reduced bone marrow hematopoietic stem cell population. Importantly, whilst the hematopoietic abnormalities are corrected as mice age, our studies reveal a postnatal window during which offspring of ACKR3 blocker treated mice are unable to mount effective inflammatory responses to inflammatory/infectious stimuli. Overall, these data demonstrate that ACKR3 is essential for preventing CXCL12 transfer from mother to embryo and for ensuring properly regulated CXCL12 control over the development of the hematopoietic system.
Keyphrases
- bone marrow
- stem cells
- high fat diet induced
- mesenchymal stem cells
- hematopoietic stem cell
- angiotensin converting enzyme
- pregnancy outcomes
- preterm infants
- genome wide
- poor prognosis
- low birth weight
- gestational age
- electronic health record
- pregnant women
- transcription factor
- type diabetes
- single cell
- insulin resistance
- skeletal muscle
- adipose tissue
- wild type
- data analysis
- metabolic syndrome
- copy number
- deep learning
- preterm birth