PT  - JOURNAL ARTICLE
AU  - Amichay Afriat
AU  - Vanessa Zuzarte-Luís
AU  - Keren Bahar Halpern
AU  - Lisa Buchauer
AU  - Sofia Marques
AU  - Aparajita Lahree
AU  - Ido Amit
AU  - Maria M. Mota
AU  - Shalev Itzkovitz
TI  - A spatiotemporally resolved single cell atlas of the <em>Plasmodium</em> liver stage
AID  - 10.1101/2021.12.03.471111
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.03.471111
4099  - http://biorxiv.org/content/early/2021/12/03/2021.12.03.471111.short
4100  - http://biorxiv.org/content/early/2021/12/03/2021.12.03.471111.full
AB  - Malaria infection involves an obligatory, yet clinically silent liver stage1,2. Hepatocytes operate in repeating units termed lobules, exhibiting heterogeneous gene expression patterns along the lobule axis3, but the effects of hepatocyte zonation on parasite development have not been molecularly explored. Here, we combine single-cell RNA sequencing4 and single-molecule transcript imaging5 to characterize the host’s and parasite’s temporal expression programs in a zonally-controlled manner for the rodent malaria parasite Plasmodium berghei ANKA. We identify differences in parasite gene expression in distinct zones, and a sub-population of periportally-biased hepatocytes that harbor abortive infections associated with parasitophorous vacuole breakdown. These ‘abortive hepatocytes’ up-regulate immune recruitment and key signaling programs. They exhibit reduced levels of Plasmodium transcripts, perturbed parasite mRNA localization, and may give rise to progressively lower abundance of periportal infections. Our study provides a resource for understanding the liver stage of Plasmodium infection at high spatial resolution and highlights heterogeneous behavior of both the parasite and the host hepatocyte.Competing Interest StatementThe authors have declared no competing interest.