Advanced

Molecular mechanisms underlying lineage bias in aging hematopoiesis

Elias, Harold K.; Bryder, David LU and Park, Christopher Y. (2017) In Seminars in Hematology 54(1). p.4-11
Abstract

Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age.  This age-associated shift in lineage potential is associated with decreased cellular... (More)

Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age.  This age-associated shift in lineage potential is associated with decreased cellular immunity and increased incidence of diseases with prominent inflammatory components including atherosclerosis, autoimmunity, neurodegenerative disease, and carcinogenesis. Understanding the molecular mechanisms that regulate this shift in linage bias therefore represents an important area of investigation in numerous human diseases.  In this review, we summarize our current understanding of the cell-intrinsic (autonomous) and cell-extrinsic factors that regulate HSC lineage fate bias during aging.  In addition, we have attempted to bring attention to important caveats and unanswered questions related to the issue of HSC lineage bias to encourage explorations of these important lines of inquiry. Ultimately, we expect a comprehensive understanding of HSC lineage bias during aging to have important implications for human health, since strategies to alter lineage bias in old HSCs not only has the potential to restore immune function in the elderly, but also to reduce the incidence of inflammation-associated diseases, many for which there is a current unmet need for novel and more effective treatments.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aging, Cell-intrinsic, Clonal hematopoiesis, Deterministic, Hematopoietic stem cell, Lineage bias
in
Seminars in Hematology
volume
54
issue
1
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85009080571
  • wos:000393445800002
ISSN
0037-1963
DOI
10.1053/j.seminhematol.2016.11.002
language
English
LU publication?
yes
id
50a2b94d-60bd-4b67-a3a0-dd5deef6ff5c
date added to LUP
2017-02-01 15:25:03
date last changed
2018-04-15 04:40:29
@article{50a2b94d-60bd-4b67-a3a0-dd5deef6ff5c,
  abstract     = {<p>Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age.  This age-associated shift in lineage potential is associated with decreased cellular immunity and increased incidence of diseases with prominent inflammatory components including atherosclerosis, autoimmunity, neurodegenerative disease, and carcinogenesis. Understanding the molecular mechanisms that regulate this shift in linage bias therefore represents an important area of investigation in numerous human diseases.  In this review, we summarize our current understanding of the cell-intrinsic (autonomous) and cell-extrinsic factors that regulate HSC lineage fate bias during aging.  In addition, we have attempted to bring attention to important caveats and unanswered questions related to the issue of HSC lineage bias to encourage explorations of these important lines of inquiry. Ultimately, we expect a comprehensive understanding of HSC lineage bias during aging to have important implications for human health, since strategies to alter lineage bias in old HSCs not only has the potential to restore immune function in the elderly, but also to reduce the incidence of inflammation-associated diseases, many for which there is a current unmet need for novel and more effective treatments.</p>},
  author       = {Elias, Harold K. and Bryder, David and Park, Christopher Y.},
  issn         = {0037-1963},
  keyword      = {Aging,Cell-intrinsic,Clonal hematopoiesis,Deterministic,Hematopoietic stem cell,Lineage bias},
  language     = {eng},
  number       = {1},
  pages        = {4--11},
  publisher    = {Elsevier},
  series       = {Seminars in Hematology},
  title        = {Molecular mechanisms underlying lineage bias in aging hematopoiesis},
  url          = {http://dx.doi.org/10.1053/j.seminhematol.2016.11.002},
  volume       = {54},
  year         = {2017},
}