Mammalian cells inherit chromosome-scale algal DNA for more than 150 cell generations, revealing an epigenetic “gatekeeper” of foreign genomes

Key findings

◆  Researchers created “planimal cells” by fusing a tiny red alga with cultured mammalian cells. One hamster-derived line retained the entire algal nuclear genome.

◆  Algal DNA was found physically linked to mammalian chromosomes. The hybrid cells continued dividing for more than 150 generations, and substantial portions of the transferred DNA persisted for 95 generations even without antibiotic selection.

◆  Most transferred algal genes remained inactive, while the foreign DNA acquired epigenetic marks that contributed to its stable maintenance in mammalian cells. This discovery opens a route toward cells that may one day use selected metabolic capabilities of algae and other organisms.

A planimal cell begins to form

Top: a small red-algal cell (appearing green in the microscope image) in contact with and fused to a much larger cultured mammalian cell. Bottom: a mammalian cell and a separate algal cell before fusion. Image: Sachihiro Matsunaga / The University of Tokyo.

 

Summary

Could a mammalian cell hold on to the chromosomes of an alga—an organism so distantly related that the two could never reproduce together? A Japanese-led research team has now demonstrated a striking answer: yes. By transferring the genetic material of a single-celled red alga into cultured mammalian cells, the researchers created experimental animal–algal hybrid cells called “planimal cells.”

The collaboration, led by Professor Sachihiro Matsunaga at the University of Tokyo together with researchers at the Institute of Science Tokyo, Kindai University, Kanagawa University, Shizuoka University, Tokyo University of Science and other institutions, found that one hamster-derived cell line retained approximately 16.3 million base pairs of algal nuclear DNA—nearly the alga’s entire nuclear genome. 

Microscopy and genome sequencing showed that algal DNA could become physically linked to mammalian chromosomes, including a site near the tip of a hamster X chromosome. The hybrid cells multiplied through more than 150 generations while retaining algal DNA. This is stable inheritance through cell division, not reproduction between an alga and an animal.

The researchers also uncovered a potential mechanism that helps mammalian cells accommodate such a large foreign genome.
Approximately 96% of the transferred algal protein-coding genes were not detectably expressed, while the imported DNA acquired epigenetic marks associated with gene silencing. The imported DNA acquired chemical and structural marks associated with gene silencing. The team calls this process “epigenetic gatekeeping,” in which the host cell helps stabilize foreign DNA while keeping most of its genes inactive.

Ultimately, the researchers hope to selectively activate useful algal genes in mammalian cells. One longer-term ambition is to combine foreign genetic information with functional cell machinery to explore photosynthesis-related functions, biomolecule production and new forms of sustainable biotechnology. None of these new metabolic abilities was demonstrated in the cells described in this study.

The findings are published in Nature Communications on 12 November 2026.

Figure 1 | Chromosomes of a planimal cell

Blue: hamster chromosomes; green: algal genomic DNA detected by fluorescence in situ hybridization; magenta: interstitial telomeric repeat sequences naturally present in hamster chromosomes. Algal-derived DNA is visible at sites on mammalian chromosomes; The magenta signal also serves as an internal control for the fluorescence in situ hybridization (FISH) experiment. Image: Sachihiro Matsunaga / The University of Tokyo.

 

Research details

(1) Background

Plants and algae can capture light energy and use carbon dioxide to synthesize organic molecules. Mammals, by contrast, normally obtain the organic compounds they need by consuming or processing material made by other organisms. What would it take to bring some of the metabolic capabilities of these very different forms of life into a single cell?

Prof. Matsunaga proposed the name “planimal” in 2018 by combining “plant” and “animal.” The long-term idea is to build experimental cells that retain properties of animal cells while eventually gaining selected functions normally associated with plants or algae. A critical first step is not to make an animal photosynthesize, but to learn whether a mammalian cell can accommodate a genome from a distant eukaryotic organism at all.

(2) Research findings

The researchers used Cyanidioschyzon merolae, commonly called schyzon, a minute single-celled red alga with an exceptionally compact nuclear genome organized into 20 chromosomes. They introduced algal material into Chinese hamster ovary (CHO-K1) and human cultured cells. Most of the detailed work used polyethylene glycol–mediated cell fusion; the team also demonstrated lower-frequency transfer following the uptake of intact algal cells.

By fluorescently tracking marked algal DNA, the researchers observed signals appearing in the mammalian nuclear environment during the first 48 hours after fusion. The experiments provided an unusual direct view of the early stages of horizontal gene transfer, in which DNA moves between unrelated organisms rather than passing from parent to offspring.

A planimal cell line remained in culture through the 155th cell generation while retaining much of its imported genome. Substantial portions of algal DNA were still detected after 95 generations without antibiotic selection. Certain regions increased in relative copy number during continued culture, although the patterns varied among planimal cell lines. These observations show that the long-term fate of foreign DNA depends on how it is accommodated in a given cellular context.

 

Figure 2 | Proliferating planimal cells

The green fluorescence comes from a reporter gene carried on transferred algal DNA and expressed in the mammalian cells. Fluorescence can still be observed after cell division, consistent with inheritance of algal-derived DNA by daughter cells. Image: Sachihiro Matsunaga / The University of Tokyo.

 

The team then asked how mammalian cells tolerate so much foreign DNA without losing the ability to grow. RNA sequencing showed that approximately 96% of the transferred algal protein-coding genes were transcriptionally silent under the conditions tested. Over time, the algal DNA acquired increased DNA methylation and repressive histone modifications, becoming enriched in heterochromatin-like regions associated with the host nuclear architecture.

When the researchers disrupted DNMT3A, a mammalian enzyme involved in establishing DNA methylation, the stable establishment and long-term maintenance of algal DNA were impaired. These results support an “epigenetic gatekeeping” model: the mammalian cell can accommodate large quantities of unfamiliar DNA while keeping most of its genes inactive. The mechanism helps explain how two distantly related genomes can persist inside a single proliferating cell.

(3) Future directions

The next challenge is to move from maintaining algal DNA to using it. Rather than introducing each useful gene into animal cells one by one, the researchers envision transferring an extensive repertoire of genes and subsequently activating selected pathways. This would be a new direction for designing experimental cells with combinations of biological functions not normally found together.

Photosynthesis-related functions are an especially ambitious target. The research team previously introduced isolated algal chloroplasts into cultured animal cells and observed photosystem II activity for at least two days. Sustained photosynthesis would also require functional chloroplasts, appropriate gene regulation and a working partnership between the host cell and its foreign machinery: possession of algal DNA alone is not enough.

Other long-term directions include producing useful biomolecules and exploring ways for engineered cells to utilize carbon dioxide. Such applications are future research goals, not capabilities demonstrated by the present planimal cells. If these technical barriers can be overcome, planimal cells may open new opportunities in synthetic biology, biomanufacturing and sustainability.

 

Related information

Previous press release
“Successful transplantation of photosynthetically active chloroplasts into animal cells: a step toward photosynthetic animal cells” (31 October 2024)
https://www.k.u-tokyo.ac.jp/information/category/press/11214.html

Origin of the planimal concept and related reading
Matsunaga, S. (2018). CYTOLOGIA, 83(1), 3–6.
https://www.jstage.jst.go.jp/article/cytologia/83/1/83_830103/_article/-char/ja

Morgado-Palacin, L. (2022). Journal of Cell Biology, 221(12), e202211043.
https://rupress.org/jcb/article/221/12/e202211043/213701/Sachihiro-Matsunaga-FISHing-the-nuclear

Related University of Tokyo lecture
“Research and ethical boundaries arising from the fusion of plants and animals” (University of Tokyo Public Lecture No. 135).
https://tv.he.u-tokyo.ac.jp/lecture_6028/

 

Publication information

Journal: Nature Communications

Article title: Epigenetic gatekeeping enables genome-scale horizontal gene transfer in eukaryotic cells

Authors: Ryota Aoki, Hidenori Nishihara, Takuya Sakamoto, Yuko Sato, Tae Kuramoto, Makiha Fukuda, Tomoko M. Matsunaga, Ayami Uehara, Daniel Slane, Yuki Kawanishi, Shunnosuke Mori, Daiki Nagaoka, Mayumi Hirakawa, Hengbin Gao, Daiki Maejima, Yuki Minoura, Yumiko Suto, Kotaro Ishii, Colin J. Anthony, Sumire Ishiyama, Shoichi Kato, Yayoi Inui, Naoki Wada, Yuko Mogi, Yamato Yoshida, Motomichi Matsuzaki, Takamasa Suzuki, Tsuneyoshi Kuroiwa, Yasuyuki Ohkawa, Tomokatsu Ikawa, Ryan Lister, Shinichiro Maruyama, Hiroshi Kimura and Sachihiro Matsunaga (corresponding author).

DOI and article link: https://doi.org/10.1038/s41467-026-78753-w

 

Glossary

1. Planimal cell
A name proposed by Prof. Sachihiro Matsunaga in 2018, from “plant” and “animal.” It describes an experimental cell intended to combine animal-cell properties with genetic material or selected functions from plants or algae. The cells in this study are laboratory-grown mammalian cell lines containing transferred algal DNA.

2. Synthetic biology
A field that studies and redesigns biological systems by assembling, modifying or combining biological components to understand living processes or create new functions.

3. Schyzon (Cyanidioschyzon merolae)
A tiny, single-celled red alga originally isolated from acidic hot-spring environments. It has a comparatively compact nuclear genome of 20 chromosomes and is useful for research on chromosomes and cell organelles.

4. Horizontal gene transfer
The movement of genetic material between organisms through routes other than the usual parent-to-offspring inheritance. This study follows experimental genome-scale transfer between distantly related eukaryotic cells.

5. Host cell
The cell that receives foreign material. Here, the host is a cultured mammalian cell that takes up DNA originating from the red alga.

6. DNA methylation
A chemical modification in which methyl groups are added to DNA. It can influence gene activity and chromatin behavior without changing the DNA sequence itself.

7. Heterochromatin
A relatively condensed form of DNA–protein packaging in the cell nucleus. Genes within these regions are often expressed at low levels or remain silent.

8. Epigenetics
Mechanisms that influence the activity or organization of genes without changing their underlying DNA sequence, including DNA methylation and chemical modifications of histone proteins.

9. Epigenetic gatekeeping
The model proposed by the researchers in which host-cell epigenetic mechanisms contribute to the accommodation and stable retention of a large foreign genome while repressing much of its gene activity.

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