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Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus

Current scheme of haematopoiesis. LT-HSC, long-term hematopoietic stem cell; MPP. Multipotent progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte erythroid progenitor; GMP, granulocyte macrophage progenitor; NK/TP, NK/T progenitor, which have NK, T, and myeloid cell potentials. Pro-T and Pro-B are progenitor cells that go through several stages to eventually produce T and B cells. Arrows indicate cell differentiation.
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Fig2: Current scheme of haematopoiesis. LT-HSC, long-term hematopoietic stem cell; MPP. Multipotent progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte erythroid progenitor; GMP, granulocyte macrophage progenitor; NK/TP, NK/T progenitor, which have NK, T, and myeloid cell potentials. Pro-T and Pro-B are progenitor cells that go through several stages to eventually produce T and B cells. Arrows indicate cell differentiation.

Mentions: HSCs are a heterogeneous pluripotent population and are composed of long-term HSC and short-term HSC. Long-term HSCs are capable of self-renew for the whole life of the host, whereas short-term HSCs retain self-renewal capacity for approximately 8 weeks [53]. Short-term HSCs proliferate and differentiate to multipotent progenitors (MPP) that give rise to common myeloid progenitors (CMP) and common lymphoid progenitors (CLP). CMP give rise to granulocyte macrophage progenitors (GMP) and megakaryocyte erythroid progenitors (MEPs) [54]. GMP can differentiate towards neutrophils, monocytes, macrophages, eosinophils, basophils, and mast cells, while MEP generate megakaryocytes and erythrocytes [55]. In contrast, CLP are restricted to give rise to T cells, B cells, Natural Killer (NK) cells, and some dendritic cells, but two studies suggest that some progenitors derived from CLP retain myeloid differentiation potentials (Figure 2) [56, 57]. However, cell lineage can be studied by over-expression or inactivation of some key transcriptional factors in hematopoietic lineages [58]. Ectopic expression of Gata1 forced primary myeloid progenitors differentiate to erythroid, eosinophil, and basophil-like cell lineages, instead of macrophages and granulocytes [59]. Similarly, expression of PU.1 and C/EBPα in early mouse T cells endows the lymphoid T cell with myeloid differentiation potential [56]. B and T lymphocytes can be reprogrammed to myeloid cells upon over expressing PU.1, C/EBPα and/or C/EBPβ [60, 61].Figure 2


Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Current scheme of haematopoiesis. LT-HSC, long-term hematopoietic stem cell; MPP. Multipotent progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte erythroid progenitor; GMP, granulocyte macrophage progenitor; NK/TP, NK/T progenitor, which have NK, T, and myeloid cell potentials. Pro-T and Pro-B are progenitor cells that go through several stages to eventually produce T and B cells. Arrows indicate cell differentiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230505&req=5

Fig2: Current scheme of haematopoiesis. LT-HSC, long-term hematopoietic stem cell; MPP. Multipotent progenitor; CMP, common myeloid progenitor; CLP, common lymphoid progenitor; MEP, megakaryocyte erythroid progenitor; GMP, granulocyte macrophage progenitor; NK/TP, NK/T progenitor, which have NK, T, and myeloid cell potentials. Pro-T and Pro-B are progenitor cells that go through several stages to eventually produce T and B cells. Arrows indicate cell differentiation.
Mentions: HSCs are a heterogeneous pluripotent population and are composed of long-term HSC and short-term HSC. Long-term HSCs are capable of self-renew for the whole life of the host, whereas short-term HSCs retain self-renewal capacity for approximately 8 weeks [53]. Short-term HSCs proliferate and differentiate to multipotent progenitors (MPP) that give rise to common myeloid progenitors (CMP) and common lymphoid progenitors (CLP). CMP give rise to granulocyte macrophage progenitors (GMP) and megakaryocyte erythroid progenitors (MEPs) [54]. GMP can differentiate towards neutrophils, monocytes, macrophages, eosinophils, basophils, and mast cells, while MEP generate megakaryocytes and erythrocytes [55]. In contrast, CLP are restricted to give rise to T cells, B cells, Natural Killer (NK) cells, and some dendritic cells, but two studies suggest that some progenitors derived from CLP retain myeloid differentiation potentials (Figure 2) [56, 57]. However, cell lineage can be studied by over-expression or inactivation of some key transcriptional factors in hematopoietic lineages [58]. Ectopic expression of Gata1 forced primary myeloid progenitors differentiate to erythroid, eosinophil, and basophil-like cell lineages, instead of macrophages and granulocytes [59]. Similarly, expression of PU.1 and C/EBPα in early mouse T cells endows the lymphoid T cell with myeloid differentiation potential [56]. B and T lymphocytes can be reprogrammed to myeloid cells upon over expressing PU.1, C/EBPα and/or C/EBPβ [60, 61].Figure 2

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus