Regulation of hematopoiesis during human development remains poorly defined. Here we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to over 8,000 human immunophenotypic blood cells from fetal liver and bone marrow. We inferred their differentiation trajectory and identified three highly proliferative oligopotent progenitor populations downstream of hematopoietic stem cells (HSCs)/multipotent progenitors (MPPs). Along this trajectory, we observed opposing patterns of chromatin accessibility and differentiation that coincided with dynamic changes in the activity of distinct lineage-specific transcription factors. Integrative analysis of chromatin accessibility and gene expression revealed extensive epigenetic but not transcriptional priming of HSCs/MPPs prior to their lineage commitment. Finally, we refined and functionally validated the sorting strategy for the HSCs/MPPs and achieved around 90% enrichment. Our study provides a useful framework for future investigation of human developmental hematopoiesis in the context of blood pathologies and regenerative medicine. Ranzoni et al. provide a detailed transcriptional and chromatin accessibility map of fetal liver and bone marrow hematopoietic stem cells (HSCs). Within HSCs, they revealed extensive epigenetic but not transcriptional priming. They identified transcriptional and functional differences between HSCs from liver and bone marrow.

(2021). Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis [journal article - articolo]. In CELL STEM CELL. Retrieved from http://hdl.handle.net/10446/178100

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis

Tangherloni, Andrea;
2021

Abstract

Regulation of hematopoiesis during human development remains poorly defined. Here we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to over 8,000 human immunophenotypic blood cells from fetal liver and bone marrow. We inferred their differentiation trajectory and identified three highly proliferative oligopotent progenitor populations downstream of hematopoietic stem cells (HSCs)/multipotent progenitors (MPPs). Along this trajectory, we observed opposing patterns of chromatin accessibility and differentiation that coincided with dynamic changes in the activity of distinct lineage-specific transcription factors. Integrative analysis of chromatin accessibility and gene expression revealed extensive epigenetic but not transcriptional priming of HSCs/MPPs prior to their lineage commitment. Finally, we refined and functionally validated the sorting strategy for the HSCs/MPPs and achieved around 90% enrichment. Our study provides a useful framework for future investigation of human developmental hematopoiesis in the context of blood pathologies and regenerative medicine. Ranzoni et al. provide a detailed transcriptional and chromatin accessibility map of fetal liver and bone marrow hematopoietic stem cells (HSCs). Within HSCs, they revealed extensive epigenetic but not transcriptional priming. They identified transcriptional and functional differences between HSCs from liver and bone marrow.
articolo
Ranzoni, Anna Maria; Tangherloni, Andrea; Berest, Ivan; Riva, Simone Giovanni; Myers, Brynelle; Strzelecka, Paulina M.; Xu, Jiarui; Panada, Elisa; Mohorianu, Irina; Zaugg, Judith B.; Cvejic, Ana
(2021). Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis [journal article - articolo]. In CELL STEM CELL. Retrieved from http://hdl.handle.net/10446/178100
File allegato/i alla scheda:
File Dimensione del file Formato  
PIIS1934590920305531.pdf

accesso aperto

Versione: publisher's version - versione editoriale
Licenza: Creative commons
Dimensione del file 5.08 MB
Formato Adobe PDF
5.08 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Aisberg ©2008 Servizi bibliotecari, Università degli studi di Bergamo | Terms of use/Condizioni di utilizzo

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10446/178100
Citazioni
  • Scopus 61
  • ???jsp.display-item.citation.isi??? 52
social impact