A spatial atlas of the healthy human liver from live donors

Oran Yakubovsky; Keren Bahar Halpern; Sapir Shir; Roy Novoselsky; Amichay Afriat; Adi Egozi; Tal Barkai; Yotam Harnik; Rouven Hoefflin; Yael Korem Kohanim; Ofra Golani; Inna Goliand; Yoseph Addadi; Merav Kedmi; Hadas Keren-Shaul; Liat Fellus-Alyagor; Lena Prichislov; Dana Hirsch; Chen Mayer; Ron Pery; Niv Pencovich; Timucin Taner; Ido Nachmany; Shalev Itzkovitz

doi:10.1038/s41586-026-10377-y

A spatial atlas of the healthy human liver from live donors

Oran Yakubovsky
, Keren Bahar Halpern
, Sapir Shir
, Roy Novoselsky
, Amichay Afriat
, Adi Egozi
, Tal Barkai
, Yotam Harnik
, Rouven Hoefflin
, Yael Korem Kohanim
, Ofra Golani
, Inna Goliand
, Yoseph Addadi
, Merav Kedmi
, Hadas Keren-Shaul
, Liat Fellus-Alyagor
, Lena Prichislov
, Dana Hirsch
, Chen Mayer
, Ron Pery

Niv Pencovich, Timucin Taner, Ido Nachmany, Shalev Itzkovitz^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals. Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression^1,2. The liver, with its unique regenerative capacity, allows analysis from live healthy donors. Here, using spatial transcriptomics (Visium, Visium HD³, multiplexed error-robust fluorescence in situ hybridization (MERFISH)⁴ and PhenoCycler imaging⁵) and single-nucleus RNA sequencing⁶, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling ‘adjacent normal’ tissue. Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology. Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals. Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis.

Original language	English
Pages (from-to)	1148-1157
Journal	Nature
Volume	653
Early online date	15 Apr 2026
DOIs	https://doi.org/10.1038/s41586-026-10377-y
Publication status	Published - 28 May 2026

Funding

The authors thank R. Lapid, R. King, G. Kahila Bar-Gal, B. Rotblat, M. Zachut and J. Shpirer for their help in sourcing the non-human samples. S.I. is supported by the Helen and Martin Kimmel Award for Innovative Investigation, the Yad Abraham Research Center for Cancer Diagnostics and Therapy, the Moross Integrated Cancer Center, the Minerva Stiftung grant, a Weizmann-Sheba grant, the Israel Science Foundation grants no. 908/21 and 3663/21, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant no. 768956 and a grant from the Ministry of Innovation, Science and Technology, Israel. Y.K.K. is supported by the JSMF Postdoctoral Fellowship in Understanding Dynamic and Multi-scale Systems.

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10.1038/s41586-026-10377-yLicence: CC BY-NC-ND

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Yakubovsky, O., Bahar Halpern, K., Shir, S., Novoselsky, R., Afriat, A., Egozi, A., Barkai, T., Harnik, Y., Hoefflin, R., Korem Kohanim, Y., Golani, O., Goliand, I., Addadi, Y., Kedmi, M., Keren-Shaul, H., Fellus-Alyagor, L., Prichislov, L., Hirsch, D., Mayer, C., ... Itzkovitz, S. (2026). A spatial atlas of the healthy human liver from live donors. Nature, 653, 1148-1157. https://doi.org/10.1038/s41586-026-10377-y

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title = "A spatial atlas of the healthy human liver from live donors",

abstract = "Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals. Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression1,2. The liver, with its unique regenerative capacity, allows analysis from live healthy donors. Here, using spatial transcriptomics (Visium, Visium HD3, multiplexed error-robust fluorescence in situ hybridization (MERFISH)4 and PhenoCycler imaging5) and single-nucleus RNA sequencing6, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling {\textquoteleft}adjacent normal{\textquoteright} tissue. Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology. Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals. Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis.",

author = "Oran Yakubovsky and \{Bahar Halpern\}, Keren and Sapir Shir and Roy Novoselsky and Amichay Afriat and Adi Egozi and Tal Barkai and Yotam Harnik and Rouven Hoefflin and \{Korem Kohanim\}, Yael and Ofra Golani and Inna Goliand and Yoseph Addadi and Merav Kedmi and Hadas Keren-Shaul and Liat Fellus-Alyagor and Lena Prichislov and Dana Hirsch and Chen Mayer and Ron Pery and Niv Pencovich and Timucin Taner and Ido Nachmany and Shalev Itzkovitz",

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year = "2026",

month = may,

day = "28",

doi = "10.1038/s41586-026-10377-y",

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Yakubovsky, O, Bahar Halpern, K , Shir, S , Novoselsky, R, Afriat, A, Egozi, A, Barkai, T, Harnik, Y , Hoefflin, R , Korem Kohanim, Y , Golani, O , Goliand, I , Addadi, Y, Kedmi, M, Keren-Shaul, H , Fellus-Alyagor, L, Prichislov, L, Hirsch, D, Mayer, C, Pery, R, Pencovich, N, Taner, T, Nachmany, I & Itzkovitz, S 2026, 'A spatial atlas of the healthy human liver from live donors', Nature, vol. 653, pp. 1148-1157. https://doi.org/10.1038/s41586-026-10377-y

TY - JOUR

T1 - A spatial atlas of the healthy human liver from live donors

AU - Yakubovsky, Oran

AU - Bahar Halpern, Keren

AU - Shir, Sapir

AU - Novoselsky, Roy

AU - Afriat, Amichay

AU - Egozi, Adi

AU - Barkai, Tal

AU - Harnik, Yotam

AU - Hoefflin, Rouven

AU - Korem Kohanim, Yael

AU - Golani, Ofra

AU - Goliand, Inna

AU - Addadi, Yoseph

AU - Kedmi, Merav

AU - Keren-Shaul, Hadas

AU - Fellus-Alyagor, Liat

AU - Prichislov, Lena

AU - Hirsch, Dana

AU - Mayer, Chen

AU - Pery, Ron

AU - Pencovich, Niv

AU - Taner, Timucin

AU - Nachmany, Ido

AU - Itzkovitz, Shalev

PY - 2026/5/28

Y1 - 2026/5/28

N2 - Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals. Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression1,2. The liver, with its unique regenerative capacity, allows analysis from live healthy donors. Here, using spatial transcriptomics (Visium, Visium HD3, multiplexed error-robust fluorescence in situ hybridization (MERFISH)4 and PhenoCycler imaging5) and single-nucleus RNA sequencing6, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling ‘adjacent normal’ tissue. Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology. Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals. Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis.

AB - Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals. Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression1,2. The liver, with its unique regenerative capacity, allows analysis from live healthy donors. Here, using spatial transcriptomics (Visium, Visium HD3, multiplexed error-robust fluorescence in situ hybridization (MERFISH)4 and PhenoCycler imaging5) and single-nucleus RNA sequencing6, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling ‘adjacent normal’ tissue. Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology. Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals. Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis.

UR - https://www.scopus.com/pages/publications/105035798929

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DO - 10.1038/s41586-026-10377-y

M3 - Article

AN - SCOPUS:105035798929

SN - 0028-0836

VL - 653

SP - 1148

EP - 1157

JO - Nature

JF - Nature

ER -

A spatial atlas of the healthy human liver from live donors

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