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An interactive resource of molecular signalling in the developing human haematopoietic stem cell niche.

Crosse, EI ; Binagui-Casas, A ; et al.
In: Development (Cambridge, England), Jg. 150 (2023-12-01), Heft 23
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The emergence of definitive human haematopoietic stem cells (HSCs) from Carnegie Stage (CS) 14 to CS17 in the aorta-gonad-mesonephros (AGM) region is a tightly regulated process. Previously, we conducted spatial transcriptomic analysis of the human AGM region at the end of this period (CS16/CS17) and identified secreted factors involved in HSC development. Here, we extend our analysis to investigate the progression of dorso-ventral polarised signalling around the dorsal aorta over the entire period of HSC emergence. Our results reveal a dramatic increase in ventral signalling complexity from the CS13-CS14 transition, coinciding with the first appearance of definitive HSCs. We further observe stage-specific changes in signalling up to CS17, which may underpin the step-wise maturation of HSCs described in the mouse model. The data-rich resource is also presented in an online interface enabling in silico analysis of molecular interactions between spatially defined domains of the AGM region. This resource will be of particular interest for researchers studying mechanisms underlying human HSC development as well as those developing in vitro methods for the generation of clinically relevant HSCs from pluripotent stem cells.

Competing Interests: Competing interests The authors declare no competing or financial interests.

(© 2023. Published by The Company of Biologists Ltd.)

Titel:
An interactive resource of molecular signalling in the developing human haematopoietic stem cell niche.
Autor/in / Beteiligte Person: Crosse, EI ; Binagui-Casas, A ; Gordon-Keylock, S ; Rybtsov, S ; Tamagno, S ; Olofsson, D ; Anderson, RA ; Medvinsky, A
Link:
Zeitschrift: Development (Cambridge, England), Jg. 150 (2023-12-01), Heft 23
Veröffentlichung: Cambridge Eng : Company Of Biologists Limited ; <i>Original Publication</i>: [Cambridge] : Company of Biologists, [c1987-, 2023
Medientyp: academicJournal
ISSN: 1477-9129 (electronic)
DOI: 10.1242/dev.201972
Schlagwort:
  • Mice
  • Animals
  • Humans
  • Cell Communication
  • Gene Expression Profiling
  • Aorta
  • Mesonephros
  • Gonads
  • Hematopoiesis genetics
  • Signal Transduction genetics
  • Hematopoietic Stem Cells
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article
  • Language: English
  • [Development] 2023 Dec 01; Vol. 150 (23). <i>Date of Electronic Publication: </i>2023 Dec 06.
  • MeSH Terms: Signal Transduction* / genetics ; Hematopoietic Stem Cells* ; Mice ; Animals ; Humans ; Cell Communication ; Gene Expression Profiling ; Aorta ; Mesonephros ; Gonads ; Hematopoiesis / genetics
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  • Grant Information: United Kingdom WT_ Wellcome Trust; MR/V030043/1 United Kingdom MRC_ Medical Research Council
  • Contributed Indexing: Keywords: AGM region; Haematopoiesis; Human development; Single cell RNA-seq; Spatial transcriptomics
  • Entry Date(s): Date Created: 20231016 Date Completed: 20231207 Latest Revision: 20240320
  • Update Code: 20240320
  • PubMed Central ID: PMC10730088

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