KOLF2.1J reference stem cell line

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Cory Pantazis (first author), Cornelis Blauwendraat, Justin McDonough and over 100 co-authors; the paper links the work to the NIH Center for Alzheimer's and Related Dementias (CARD). Cell Stem Cell 29(12):1685–1702, 1 Dec 2022. The paper's grants include NIH institutes (NIA, NINDS, NIGMS, intramural NIH), Wellcome, the MRC, the European Research Council and ZonMw. The Jackson Laboratory (JAX) distributes the line. JAX lists the Chan Zuckerberg Initiative, ASAP and the NIH as funders of its catalogue of edited lines.

What happened

Patient-derived stem cells (landmark 47) differ in thousands of ways from line to line, so a result in one lab often fails in another. Gene editing in a single background (landmark 272) fixes part of this, but each lab still picked its own line. The team sub-cloned candidate lines and read their whole genomes. They tested how stable each stayed after CRISPR-Cas9 editing and how well each became common cell types. Nine parental lines were curated and eight sub-lines tested.

KOLF2.1J is a genetically male line of European ancestry. It descends from KOLF2-C1; the team used CRISPR to correct a mutation in one copy of ARID2, and found no rare, damaging variants among the 25 coding variants unique to KOLF2.1J. Nine other groups then tested it against 12 other lines across 10 protocols or assays. The sample read reported no significant differences from the comparison lines in several assays (germ layers, microglia) and small differences in others (for example higher S100β in astrocytes, lower evoked currents in NGN2 cortical neurons). Dopaminergic progenitors, neurons and organoids were made from it, and a Parkinson's polygenic risk score fell within the expected population range.

The paper presents KOLF2.1J as the parent of the iPSC Neurodegenerative Disease Initiative (iNDI), a CARD project that edits disease variants into it; the JAX catalogue gives "more than 100" variants in 73 genes on one page and "134" on another. Parkinson's-specific lines (iNDI-PD, ASAP-funded) were listed by MJFF as still in development, so their count and release are not confirmed here.

Why it moved us toward a cure

A shared background lets many labs test the same mutation in the same cells, which should make model results easier to compare and replicate. It sits beside the single-lab design of landmark 272 and the 65-line collection in landmark 273, which uses a different, embryonic line. On 24 Aug 2026 JAX announced a $4.6 million ASAP Collaborative Research Network technical-track grant, shared with the New York Stem Cell Foundation, to build more than 20 new Parkinson's-related lines, all on KOLF2.1J.

Outcome

Advanced. The line is distributed and a funded Parkinson's extension has started. It is still a young, single-donor line grown in a dish, so it cannot show ageing or the effect of other cell types, and no therapy has come from it.

Sources

• Pantazis et al., Cell Stem Cell 2022;29:1685–1702, DOI 10.1016/j.stem.2022.11.004, PMID 36459969 (abstract via Europe PMC, full text PMC9782786)
• JAX iPSC catalogue (iNDI)
• JAX release, 24 Aug 2026: ASAP grant to JAX and NYSCF
• Not yet verified: the donor's age and origin (HipSci or other) and the exact nature of the ARID2 change (the page read says "correct a mutation"); individual author roles; the count and release dates of iNDI-PD lines (MJFF's catalogue entries were seen only through a search summary); the 100 versus 134 variant figure.