scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes

Abstract A population of CD133+lin-CD45- and CD34+lin-CD45- very small embryonic-like stem cells (VSELs) has been identified in postnatal human tissues, including bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Under appropriate conditions, VSELs in vitro and in vi...

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Main Authors: Justyna Jarczak, Kamila Bujko, Mariusz Z. Ratajczak, Magdalena Kucia
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-79810-4
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author Justyna Jarczak
Kamila Bujko
Mariusz Z. Ratajczak
Magdalena Kucia
author_facet Justyna Jarczak
Kamila Bujko
Mariusz Z. Ratajczak
Magdalena Kucia
author_sort Justyna Jarczak
collection DOAJ
description Abstract A population of CD133+lin-CD45- and CD34+lin-CD45- very small embryonic-like stem cells (VSELs) has been identified in postnatal human tissues, including bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Under appropriate conditions, VSELs in vitro and in vivo differentiate into tissue-committed stem cells for all three germ layers. Molecular analysis of adult murine BM-purified VSELs revealed that these rare cells deposited during development in adult tissues (i) express a similar transcriptome as embryonic stem cells, (ii) share several markers characteristic for epiblast and migratory primordial germ cells (PGCs), (iii) highly express a polycomb group protein enhancer of zeste drosophila homolog 2 (Ezh2) and finally (iv) display a unique pattern of imprinting at crucial paternally inherited genes that promotes their quiescence. Here, by employing single-cell RNA sequencing we demonstrate for the first time that purified from UCB human VSELs defined by expression of CD34 or CD133 antigens and lack of lineage markers, including CD45 antigen express similar molecular signature as murine BM-derived VSELs. Specifically, unsupervised clustering revealed numerous subpopulations of VSELs including ones i) annotated to germline compartments, ii) regulated by parental imprinting, iii) responding to early developmental fate decisions, iv) transcription factors involved in differentiation and development, including homeobox family of genes, and v) expressing innate immunity and purinergic signaling genes.
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spelling doaj-art-9ec09a53cee44e68954a6eca17af50fd2025-08-20T02:49:14ZengNature PortfolioScientific Reports2045-23222024-11-0114111910.1038/s41598-024-79810-4scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genesJustyna Jarczak0Kamila Bujko1Mariusz Z. Ratajczak2Magdalena Kucia3Laboratory of Regenerative Medicine, Center for Preclinical Studies and Technology, Medical University of WarsawLaboratory of Regenerative Medicine, Center for Preclinical Studies and Technology, Medical University of WarsawLaboratory of Regenerative Medicine, Center for Preclinical Studies and Technology, Medical University of WarsawLaboratory of Regenerative Medicine, Center for Preclinical Studies and Technology, Medical University of WarsawAbstract A population of CD133+lin-CD45- and CD34+lin-CD45- very small embryonic-like stem cells (VSELs) has been identified in postnatal human tissues, including bone marrow (BM), mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Under appropriate conditions, VSELs in vitro and in vivo differentiate into tissue-committed stem cells for all three germ layers. Molecular analysis of adult murine BM-purified VSELs revealed that these rare cells deposited during development in adult tissues (i) express a similar transcriptome as embryonic stem cells, (ii) share several markers characteristic for epiblast and migratory primordial germ cells (PGCs), (iii) highly express a polycomb group protein enhancer of zeste drosophila homolog 2 (Ezh2) and finally (iv) display a unique pattern of imprinting at crucial paternally inherited genes that promotes their quiescence. Here, by employing single-cell RNA sequencing we demonstrate for the first time that purified from UCB human VSELs defined by expression of CD34 or CD133 antigens and lack of lineage markers, including CD45 antigen express similar molecular signature as murine BM-derived VSELs. Specifically, unsupervised clustering revealed numerous subpopulations of VSELs including ones i) annotated to germline compartments, ii) regulated by parental imprinting, iii) responding to early developmental fate decisions, iv) transcription factors involved in differentiation and development, including homeobox family of genes, and v) expressing innate immunity and purinergic signaling genes.https://doi.org/10.1038/s41598-024-79810-4Umbilical cord blood VSELsSingle cell sequencingRNA sequencingAdult stem cellsPluripotencyTranscriptome
spellingShingle Justyna Jarczak
Kamila Bujko
Mariusz Z. Ratajczak
Magdalena Kucia
scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
Scientific Reports
Umbilical cord blood VSELs
Single cell sequencing
RNA sequencing
Adult stem cells
Pluripotency
Transcriptome
title scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
title_full scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
title_fullStr scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
title_full_unstemmed scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
title_short scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
title_sort scrna seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes
topic Umbilical cord blood VSELs
Single cell sequencing
RNA sequencing
Adult stem cells
Pluripotency
Transcriptome
url https://doi.org/10.1038/s41598-024-79810-4
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