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Embryonic endothelial evolution towards first hematopoietic stem cells revealed by single-cell transcriptomic and functional analyses.

ABSTRACT: Hematopoietic stem cells (HSCs) in adults are believed to be born from hemogenic endothelial cells (HECs) in mid-gestational embryos. Due to the rare and transient nature, the HSC-competent HECs have never been stringently identified and accurately captured, let alone their genuine vascular precursors. Here, we first used high-precision single-cell transcriptomics to unbiasedly examine the relevant EC populations at continuous developmental stages with intervals of 0.5 days from embryonic day (E) 9.5 to E11.0. As a consequence, we transcriptomically identified two molecularly different arterial EC populations and putative HSC-primed HECs, whose number peaked at E10.0 and sharply decreased thereafter, in the dorsal aorta of the aorta-gonad-mesonephros (AGM) region. Combining computational prediction and in vivo functional validation, we precisely captured HSC-competent HECs by the newly constructed Neurl3-EGFP reporter mouse model, and realized the enrichment further by a combination of surface markers (Procr⁺Kit⁺CD44⁺, PK44). Surprisingly, the endothelial-hematopoietic dual potential was rarely but reliably witnessed in the cultures of single HECs. Noteworthy, primitive vascular ECs from E8.0 experienced two-step fate choices to become HSC-primed HECs, namely an initial arterial fate choice followed by a hemogenic fate conversion. This finding resolves several previously observed contradictions. Taken together, comprehensive understanding of endothelial evolutions and molecular programs underlying HSC-primed HEC specification in vivo will facilitate future investigations directing HSC production in vitro.

SUBMITTER: Hou S

PROVIDER: S-EPMC7196075 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Grain aphid (Sitobion avenae F) and pea aphid (Acyrthosiphon pisum) are two agriculturally important pest species, which cause significant yield losses to crop plants each year by inflicting damage both through the direct effects of feeding and by vectoring debilitating plant viruses. Although a close phylogenetic relationship between grain aphid and pea aphid was proposed, the biological variations between these two aphid species are obvious. While the host ranges of grain aphid is restricted to cereal crops and in particular wheat, that of pea aphid is wider, mainly colonizing leguminous plant species. Until now, the genetic factors underlying the divergence between grain aphid and pea aphid still remain unclear due to the limited genomic data of grain aphid available in public databases.Based on a set of transcriptome data of grain aphid generated by using Roche 454 GS-FLX pyrosequencing, comparative analysis between this set of transcriptome data of grain aphid and mRNA sequences of pea aphid available in the public databases was performed. Compared with mRNA sequences of pea aphid, 4,857 unigenes were found to be specifically presented in the transcriptome of grain aphid under the rearing conditions described in this study. Furthermore, 3,368 orthologous pairs which could be calculated with both nonsynonymous (Ka) and synonymous (Ks) substitutions were used to infer their sequence divergences. The average differences in the coding, 5' and 3' untranslated regions of these orthologs were 10.53%, 21.29% and 18.96%, respectively. Moreover, of 340 orthologs which were identified to have evolved in response to positive selection based on the rates of Ka and Ks substitutions, 186 were predicted to be involved in secondary metabolism and xenobiotic metabolisms which might contribute to the divergence of these two aphid species.The comprehensive transcriptome divergent sequence analysis between grain aphid and pea aphid provides an invaluable resource for the investigation of genes involved in host plant adaptation and evolution. Moreover, the demonstration of divergent transcriptome sequences between grain aphid and pea aphid pave the way for the investigation of the molecular mechanisms underpinning the biological variations of these two agriculturally important aphid species.

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Embryonic endothelial evolution towards first hematopoietic stem cells revealed by single-cell transcriptomic and functional analyses.

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