A single-cell atlas of ~250,000 cells from 30 human fetal cortices (15 Down syn…

A single-cell atlas of ~250,000 cells from 30 human fetal cortices (15 Down syndrome, 15 control; 10–20 weeks postconception) identifies subtype-specific reduction of RORB+ and FOXP1+ excitatory neurons in DS, with chromosome 21 transcription factors BACH1, PKNOX1, and GABPA emerging as dosage-sensitive hubs regulating intellectual-disability-linked genes; antisense-mediated TF normalization partially rescued target gene expression.

{
  "n": 250000,
  "doi": "10.1038/s41591-026-04211-1",
  "claim": "A single-cell atlas of ~250,000 cells from 30 human fetal cortices (15 Down syndrome, 15 control; 10–20 weeks postconception) identifies subtype-specific reduction of RORB+ and FOXP1+ excitatory neurons in DS, with chromosome 21 transcription factors BACH1, PKNOX1, and GABPA emerging as dosage-sensitive hubs regulating intellectual-disability-linked genes; antisense-mediated TF normalization partially rescued target gene expression.",
  "title": null,
  "cite_key": "Lattke2026",
  "evidence": "Single-cell transcriptomic + chromatin accessibility profiling of ~250,000 cells from 15 DS and 15 control human fetal cortices; ASO TF perturbation in human neural progenitors.",
  "effect_size": null,
  "text_access": "abstract_only",
  "study_system": "human fetal cortex (10-20 weeks PCW); scRNA-seq + scATAC-seq; ASO perturbation",
  "target_section": "section_11",
  "_source_cluster": "cluster_01_molecular_taxonomy",
  "replication_status": "replication_unknown",
  "_source_cluster_index": 96,
  "claim_source_sentence": "Our analysis revealed a subtype-specific reduction in RORB- and FOXP1-expressing excitatory neurons and widespread disruption of neurodevelopmental transcriptional programs. Chromosome 21 transcription factors BACH1, PKNOX1 and GABPA emerged as dosage-sensitive hubs regulating genes linked to intellectual disability.",
  "replication_evidence_dois": [],
  "effect_size_source_sentence": null
}

[
  "paper:9354c026-33f1-4701-b47d-64ce038e7e37"
]

Our analysis revealed a subtype-specific reduction in RORB- and FOXP1-expressing excitatory neurons and widespread disruption of neurodevelopmental transcriptional programs. Chromosome 21 transcription factors BACH1, PKNOX1 and GABPA emerged as dosage-sensitive hubs regulating genes linked to intellectual disability.

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