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Biological and molecular evidence for existence of lymphoid-primed multipotent progenitors

Luc, Sidinh LU ; Buza-Vidas, Natalija LU and Jacobsen, Sten Eirik W LU (2007) In Annals of the New York Academy of Sciences 1106. p.89-94
Abstract
Studies from our and other laboratories have over the last 2 years implicated the existence of multipotent progenitors (MPPs) with combined granulocyte-macrophage, B cell, and T cell potential, but little or no megakaryocyte-erythroid (MkE) potential in the adult bone marrow Lineage (-)SCA-1 +KIT+ (LSK) compartment of multipotent stem and progenitor cells. The evidence for the existence of LSKCD34(+) FLT3(hi) lymphoid-primed MPPs (LMPPs) implicates that a strict separation into common myeloid and lymphoid pathways might not be the first lineage commitment step of hematopoietic stem cells (HSCs). Together with the evidence for existence of common myeloid and common lymphoid progenitors (CMPs and CLPs, respectively), the identification of... (More)
Studies from our and other laboratories have over the last 2 years implicated the existence of multipotent progenitors (MPPs) with combined granulocyte-macrophage, B cell, and T cell potential, but little or no megakaryocyte-erythroid (MkE) potential in the adult bone marrow Lineage (-)SCA-1 +KIT+ (LSK) compartment of multipotent stem and progenitor cells. The evidence for the existence of LSKCD34(+) FLT3(hi) lymphoid-primed MPPs (LMPPs) implicates that a strict separation into common myeloid and lymphoid pathways might not be the first lineage commitment step of hematopoietic stem cells (HSCs). Together with the evidence for existence of common myeloid and common lymphoid progenitors (CMPs and CLPs, respectively), the identification of LMPPs also suggests that at least the granulocyte-macrophage lineage can be generated through alternative pathways. However, the existence of LMPPs has recently been questioned, as there is evidence that at least a fraction of LSKCD34(+) FLT3(hi) cells sustains MkE potential. Thus, in more recent studies we have in more detail compared the molecular signature of adult LMPPs to populations of LSK cells enriched for cells with pluripotent HSC activity. Notably, we have found at the global as well as single-cell level that LMPPs when compared with pluripotent HSCs downregulate the transcriptional priming of genes typically expressed in cells of the MkE lineage, while upregulating early lymphoid genes. Although other studies have suggested that the earliest HSC commitment steps might differ in fetal and adult hematopoiesis, we have also obtained evidence suggesting that the LMPP is defined already during fetal development. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hematopoiesis, hematopoietic stem cell, lineage commitment
in
Annals of the New York Academy of Sciences
volume
1106
pages
89 - 94
publisher
New York Academy of Sciences
external identifiers
  • wos:000248195300009
  • scopus:34548435701
ISSN
0077-8923
DOI
10.1196/annals.1392.023
language
English
LU publication?
yes
id
9f02cc9b-8b33-4c34-bd44-810c16be7729 (old id 657353)
date added to LUP
2007-12-13 14:14:02
date last changed
2017-07-23 04:50:00
@article{9f02cc9b-8b33-4c34-bd44-810c16be7729,
  abstract     = {Studies from our and other laboratories have over the last 2 years implicated the existence of multipotent progenitors (MPPs) with combined granulocyte-macrophage, B cell, and T cell potential, but little or no megakaryocyte-erythroid (MkE) potential in the adult bone marrow Lineage (-)SCA-1 +KIT+ (LSK) compartment of multipotent stem and progenitor cells. The evidence for the existence of LSKCD34(+) FLT3(hi) lymphoid-primed MPPs (LMPPs) implicates that a strict separation into common myeloid and lymphoid pathways might not be the first lineage commitment step of hematopoietic stem cells (HSCs). Together with the evidence for existence of common myeloid and common lymphoid progenitors (CMPs and CLPs, respectively), the identification of LMPPs also suggests that at least the granulocyte-macrophage lineage can be generated through alternative pathways. However, the existence of LMPPs has recently been questioned, as there is evidence that at least a fraction of LSKCD34(+) FLT3(hi) cells sustains MkE potential. Thus, in more recent studies we have in more detail compared the molecular signature of adult LMPPs to populations of LSK cells enriched for cells with pluripotent HSC activity. Notably, we have found at the global as well as single-cell level that LMPPs when compared with pluripotent HSCs downregulate the transcriptional priming of genes typically expressed in cells of the MkE lineage, while upregulating early lymphoid genes. Although other studies have suggested that the earliest HSC commitment steps might differ in fetal and adult hematopoiesis, we have also obtained evidence suggesting that the LMPP is defined already during fetal development.},
  author       = {Luc, Sidinh and Buza-Vidas, Natalija and Jacobsen, Sten Eirik W},
  issn         = {0077-8923},
  keyword      = {hematopoiesis,hematopoietic stem cell,lineage commitment},
  language     = {eng},
  pages        = {89--94},
  publisher    = {New York Academy of Sciences},
  series       = {Annals of the New York Academy of Sciences},
  title        = {Biological and molecular evidence for existence of lymphoid-primed multipotent progenitors},
  url          = {http://dx.doi.org/10.1196/annals.1392.023},
  volume       = {1106},
  year         = {2007},
}