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July 31, 2021Open Access

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single cell resolution

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Authors

MAMarina AinciburuTETeresa EzpondaNBNerea Berastegui

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Overview

Single-cell profiling reveals distinct transcriptional shifts and transcription factor regulons across aging and myelodysplastic syndrome, highlighting targets for personalized therapies.

Key Points

  • Characterize cellular and transcriptomic alterations in human hematopoietic stem and progenitor cells during healthy aging and malignant transformation in myelodysplastic syndrome.
  • Performed single-cell RNA sequencing (scRNA-seq) on enriched hematopoietic stem and progenitor cell populations isolated from healthy young donors, elderly individuals, and patients with myelodysplastic syndrome.
  • Conducted trajectory inference, gene set enrichment analysis, and computational gene regulatory network reconstructions to evaluate lineage differentiation and transcription factor activity.
  • Aging shifted progenitor compartment proportions, modified differentiation trajectory dynamics, and activated distinct regulatory transcription factor networks in elderly individuals.
  • Myelodysplastic syndrome cells displayed disrupted erythroid differentiation trajectories—such as altered TRIB2 dynamics—and disease-specific activation of regulons including SMAD1, HOXA6, POU2F2, and RUNX1.

Cite This Study

Ainciburu et al. (2021) studied this question.

synapsesocial.com/papers/6a1a7ef3837f1a2c63b8b0cchttps://doi.org/10.1101/2021.07.30.454542
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