Yolk sac cell atlas reveals multiorgan functions during human early development.
Issac GohRachel Anne BottingAntony RoseSimone WebbJustin EngelbertYorick GittonEmily StephensonMariana Quiroga LondoñoMichael MatherNicole MendeIvan Imaz-RosshandlerLu YangDavid HorsfallDaniela Basurto-LozadaNana-Jane ChipampeVictoria RookJimmy Tsz Hang LeeMai-Linh Nu TonDaniel KeitleyPavel V MazinM S VijayabaskarRebecca HannahLaure GambardellaKile GreenStephane BallereauMegumi InoueElizabeth TuckValentina LorenziKwasi KwakwaClara AlsinetBayanne OlabiMohi MiahChloe AdmaneDorin-Mirel PopescuMeghan AcresDavid DixonThomas NessRowen CoulthardSteven N LisgoDeborah J HendersonEmma DannChenqu SuoSarah J KinstonJong-Eun ParkKrzysztof PolańskiJohn C MarioniStijn van DongenKerstin B MeyerMarella de BruijnJames PalisSam BehjatiElisa LaurentiNicola K WilsonRoser Vento-TormoAlain ChédotalOmer Ali BayraktarIrene RobertsLaura JardineBerthold GöttgensSarah A TeichmannMuzlifah A HaniffaPublished in: Science (New York, N.Y.) (2023)
The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.