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<p>Hemogenic endothelium (HE) is recognized as the origin of all definitive blood cells, including hematopoietic stem cells (HSCs); however, the mechanisms governing the hematopoietic progenitor versus HSC fate choice within the HE remain unknown. Here we combine differentiation assays with full-length single-cell transcriptome data for extra-embryonic yolk sac (YS) and intra-embryonic aorta–gonad–mesonephros (AGM) region HE populations. We identified and localized three differentiation trajectories, each containing a distinct HE subset: erythromyeloid progenitor-primed HE in the YS plexus, lymphomyeloid progenitor-primed HE in large YS arteries and hematopoietic stem and progenitor cell-primed HE in the AGM. Chromatin modifiers and spliceosome components were enriched in AGM HE. This correlated with a higher isoform complexity of the AGM HE transcriptome. Distinct AGM HE-specific isoform expression patterns were observed for a broad range of genes, including stemness-associated factors like <i>Runx1</i>. Our data form a unique resource for studying cell fate decisions in different HE populations.</p>

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Single-cell profiling reveals three endothelial-to-hematopoietic transitions with divergent isoform expression landscapes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月11日

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  • Wen Hao Neo,
  • Muhammad Zaki Hidayatullah Fadlullah,
  • Harshangda Bhatnagar,
  • Cristiana Barone,
  • Giulia Quattrini,
  • Filipa Timóteo-Ferreira,
  • Joana Carrelha,
  • Gianluca Sala,
  • Robert Sellers,
  • John Weightman,
  • Wolfgang Breitwieser,
  • Natalia Moncaut,
  • Roshana Thambyrajah,
  • Sten Eirik W. Jacobsen,
  • Mudassar Iqbal,
  • Syed Murtuza Baker,
  • Emanuele Azzoni,
  • Michael Lie-A-Ling,
  • Georges Lacaud

摘要

Hemogenic endothelium (HE) is recognized as the origin of all definitive blood cells, including hematopoietic stem cells (HSCs); however, the mechanisms governing the hematopoietic progenitor versus HSC fate choice within the HE remain unknown. Here we combine differentiation assays with full-length single-cell transcriptome data for extra-embryonic yolk sac (YS) and intra-embryonic aorta–gonad–mesonephros (AGM) region HE populations. We identified and localized three differentiation trajectories, each containing a distinct HE subset: erythromyeloid progenitor-primed HE in the YS plexus, lymphomyeloid progenitor-primed HE in large YS arteries and hematopoietic stem and progenitor cell-primed HE in the AGM. Chromatin modifiers and spliceosome components were enriched in AGM HE. This correlated with a higher isoform complexity of the AGM HE transcriptome. Distinct AGM HE-specific isoform expression patterns were observed for a broad range of genes, including stemness-associated factors like Runx1. Our data form a unique resource for studying cell fate decisions in different HE populations.