Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood

Andrejs Ivanovs; Stanislav Rybtsov; Richard A. Anderson; Alexander Medvinsky

doi:10.1016/j.stemcr.2020.08.008

Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood

Andrejs Ivanovs, Stanislav Rybtsov, Richard A. Anderson, Alexander Medvinsky (Corresponding Author)

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells.

Original language	English
Pages (from-to)	811-816
Number of pages	6
Journal	Stem Cell Reports
Volume	15
Issue number	4
DOIs	https://doi.org/10.1016/j.stemcr.2020.08.008
Publication status	Published - 13 Oct 2020
Externally published	Yes

Keywords*

AGM region
HSC
human
umbilical cord blood

Field of Science*

3.1 Basic medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.stemcr.2020.08.008Licence: CC BY-NC-ND

Cite this

@article{9a86c3978f65431bacf9b6bbd410d95b,

title = "Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood",

abstract = "Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells.",

keywords = "AGM region, HSC, human, umbilical cord blood",

author = "Andrejs Ivanovs and Stanislav Rybtsov and Anderson, {Richard A.} and Alexander Medvinsky",

note = "Funding Information: The authors thank the patients for donating tissues; research nurses Anne Saunderson, Joan Creiger, and Isobel Morton for patient recruitment; and the Edinburgh Reproductive Tissue Biobank for provision of fresh UCB specimens. We are grateful to Dr. Lesley Forrester and Ms. Adelle Greene for useful comments on the manuscript. This work was supported by grants from the Medical Research Council (UK) to A.M. Publisher Copyright: {\textcopyright} 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = oct,

day = "13",

doi = "10.1016/j.stemcr.2020.08.008",

language = "English",

volume = "15",

pages = "811--816",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood

AU - Ivanovs, Andrejs

AU - Rybtsov, Stanislav

AU - Anderson, Richard A.

AU - Medvinsky, Alexander

N1 - Funding Information: The authors thank the patients for donating tissues; research nurses Anne Saunderson, Joan Creiger, and Isobel Morton for patient recruitment; and the Edinburgh Reproductive Tissue Biobank for provision of fresh UCB specimens. We are grateful to Dr. Lesley Forrester and Ms. Adelle Greene for useful comments on the manuscript. This work was supported by grants from the Medical Research Council (UK) to A.M. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/13

Y1 - 2020/10/13

N2 - Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells.

AB - Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells.

KW - AGM region

KW - HSC

KW - human

KW - umbilical cord blood

UR - http://www.scopus.com/inward/record.url?scp=85091954683&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2020.08.008

DO - 10.1016/j.stemcr.2020.08.008

M3 - Article

C2 - 32946804

AN - SCOPUS:85091954683

SN - 2213-6711

VL - 15

SP - 811

EP - 816

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood

Abstract

Keywords*

Field of Science*

Publication Type*

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this