Evidence map›Paper›PMID 35355517›Full record

ArticleiScience2022

Chromosomal instability drives convergent and divergent evolution toward advantageous inherited traits in mammalian CHO bioproduction lineages.

Steve Huhn, Meiping Chang, Amit Kumar, Ren Liu, Bo Jiang, Michael Betenbaugh, Henry Lin, Gregg Nyberg, Zhimei Du

Abstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
  2. Polyploidy: A macromutational force pushing bioeconomic developments.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Steve HuhnProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Meiping ChangProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Amit KumarProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Ren LiuProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Bo JiangProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Michael BetenbaughDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Henry LinProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Gregg NybergProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
Zhimei DuProcess Cell Sciences, Biologics Process R&D, Merck & Co., Inc., Kenilworth, NJ 07033, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetic instability of Chinese hamster ovary (CHO) cells is implicated in production inconsistency through poorly defined mechanisms. Using a multi-omics approach, we analyzed the variations of CHO lineages derived from CHO-K1 cells. We identify an equilibrium between random genetic variation of the CHO genome and heritable traits driven by culture conditions, selection criteria, and genetic linkage. These inherited changes are associated with the selection pressures related to serum removal, suspension culture transition, protein expression, and secretion. We observed that a haploid reduction of a Chromosome 2 region after serum-free, suspension adaptation, was consistently inherited, suggesting common adaptation mechanisms. Genetic variations also included ∼200 insertions/deletions, ∼1000 single-nucleotide polymorphisms, and ∼300-2000 copy number variations, which were exacerbated after gene editing. In addition, heterochromatic chromosomes were preferentially lost as cells continuously evolved. Together, these observations demonstrate a highly plastic signature for adapted CHO cells and paves the way towards future host cell engineering.

Indexed as

BiotechnologyEvolutionary mechanismsGeneticsOmics

Identifiers

PMID35355517
PMCPMC8958363

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.