Detection of Hematopoietic Stem Cell Transcriptome in Human Fetal Kidneys and Kidney Organoids Derived From Human Induced Pluripotent Stem Cells.

IPSC fetal kidney hematopoietic stem cell organoid transcriptome

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2021
Historique:
received: 17 02 2021
accepted: 12 05 2021
entrez: 28 6 2021
pubmed: 29 6 2021
medline: 29 6 2021
Statut: epublish

Résumé

In mammalians, hematopoietic stem cells (HSCs) arise in the dorsal aorta from the hemogenic endothelium, followed by their migration to the fetal liver and to the bone marrow. In zebrafish, the kidney is the site of primary hematopoiesis. In humans, the presence of HSCs in the fetal or adult kidney has not been established. We analyzed the presence of HSC markers in the human fetal kidneys by analysis of single-cell datasets. We then analyzed in kidney organoids derived from induced pluripotent stem cells (iPSCs) the presence of hematopoietic markers using transcriptome analyses. Twelve clusters were identified as stromal, endothelial, and nephron cell type-specific markers in the two fetal stage (17 weeks) kidney datasets. Among these, the expression of hematopoietic cells in cluster 9 showed an expression of primitive markers. Moreover, whole transcriptome analysis of our iPSC-derived kidney organoids revealed induction of the primitive hematopoietic transcription factor RUNX1 as found in the human fetal kidney cortex. These finding support the presence of cells expressing HSC transcriptome in the human kidney. The mechanisms of the appearance of the cells with the same transcriptional features during iPSC-derived kidney organoid generation require further investigation.

Sections du résumé

BACKGROUND BACKGROUND
In mammalians, hematopoietic stem cells (HSCs) arise in the dorsal aorta from the hemogenic endothelium, followed by their migration to the fetal liver and to the bone marrow. In zebrafish, the kidney is the site of primary hematopoiesis. In humans, the presence of HSCs in the fetal or adult kidney has not been established.
METHODS METHODS
We analyzed the presence of HSC markers in the human fetal kidneys by analysis of single-cell datasets. We then analyzed in kidney organoids derived from induced pluripotent stem cells (iPSCs) the presence of hematopoietic markers using transcriptome analyses.
RESULTS RESULTS
Twelve clusters were identified as stromal, endothelial, and nephron cell type-specific markers in the two fetal stage (17 weeks) kidney datasets. Among these, the expression of hematopoietic cells in cluster 9 showed an expression of primitive markers. Moreover, whole transcriptome analysis of our iPSC-derived kidney organoids revealed induction of the primitive hematopoietic transcription factor RUNX1 as found in the human fetal kidney cortex.
CONCLUSION CONCLUSIONS
These finding support the presence of cells expressing HSC transcriptome in the human kidney. The mechanisms of the appearance of the cells with the same transcriptional features during iPSC-derived kidney organoid generation require further investigation.

Identifiants

pubmed: 34178994
doi: 10.3389/fcell.2021.668833
pmc: PMC8226023
doi:

Types de publication

Journal Article

Langues

eng

Pagination

668833

Informations de copyright

Copyright © 2021 Hwang, Desterke, Loisel-Duwattez, Griscelli, Bennaceur-Griscelli and Turhan.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Jin Wook Hwang (JW)

INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.

Christophe Desterke (C)

INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.

Julien Loisel-Duwattez (J)

INSERM U1195, AP-HP, Service de Neurologie, Faculté de Médecine, Hôpital Bicêtre, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Frank Griscelli (F)

INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.
INGESTEM National IPSC Infrastructure, Villejuif, France.
Division of Hematology, AP-HP Paris Saclay, Le Kremlin-Bicêtre, France.

Annelise Bennaceur-Griscelli (A)

INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.
INGESTEM National IPSC Infrastructure, Villejuif, France.
Division of Hematology, AP-HP Paris Saclay, Le Kremlin-Bicêtre, France.

Ali G Turhan (AG)

INSERM U935/UA09, Université Paris-Saclay, Villejuif, France.
ESTeam Paris Sud, Université Paris Sud, Villejuif, France.
INGESTEM National IPSC Infrastructure, Villejuif, France.
Division of Hematology, AP-HP Paris Saclay, Le Kremlin-Bicêtre, France.

Classifications MeSH